BACKGROUND Gastric cancer(GC)is one of the most common malignant tumors in the world,and its prognosis is closely related to many factors.In recent years,the incidence of vascular thrombosis in patients with GC has gr...BACKGROUND Gastric cancer(GC)is one of the most common malignant tumors in the world,and its prognosis is closely related to many factors.In recent years,the incidence of vascular thrombosis in patients with GC has gradually attracted increasing attention,and studies have shown that it may have a significant impact on the survival rate and prognosis of patients.However,the specific mechanism underlying the association between vascular thrombosis and the prognosis of patients with GC remains unclear.AIM To analyze the relationships between vascular cancer support and other clinicopathological factors and their influence on the prognosis of patients with GC.METHODS This study retrospectively analyzed the clinicopathological data of 621 patients with GC and divided them into a positive group and a negative group according to the presence or absence of a vascular thrombus.The difference in the 5-year cumulative survival rate between the two groups was compared,and the relationships between vascular cancer thrombus and other clinicopathological factors and their influence on the prognosis of patients with GC were analyzed.RESULTS Among 621 patients with GC,the incidence of vascular thrombi was 31.7%(197 patients).Binary logistic regression analysis revealed that the degree of tumor differentiation,depth of invasion,and extent of lymph node metastasis were independent influencing factors for the occurrence of vascular thrombi in GC patients(P<0.01).The trend of the χ^(2) test showed that the degree of differentiation,depth of invasion,and extent of lymph node metastasis were linearly correlated with the percentage of vascular thrombi in GC patients(P<0.01),and the correlation between lymph node metastasis and vascular thrombi was more significant(r=0.387).Univariate analysis revealed that the 5-year cumulative survival rate of the positive group was significantly lower than that of the negative group(46.7%vs 73.3%,P<0.01).Multivariate analysis revealed that age,tumor diameter,TNM stage,and vascular thrombus were independent risk factors for the prognosis of GC patients(all P<0.05).Further stratified analysis revealed that the 5-year cumulative survival rate of stage Ⅲ GC patients in the thrombolase-positive group was significantly lower than that in the thrombolase-negative group(36.1%vs 51.4%;P<0.05).CONCLUSION Vascular cancer status is an independent risk factor affecting the prognosis of patients with GC.The combination of vascular cancer suppositories and TNM staging can better judge the prognosis of patients with GC and guide more reasonable treatment.展开更多
BACKGROUND Gastric cancer is a leading cause of cancer-related deaths worldwide.Prognostic assessments are typically based on the tumor-node-metastasis(TNM)staging system,which does not account for the molecular heter...BACKGROUND Gastric cancer is a leading cause of cancer-related deaths worldwide.Prognostic assessments are typically based on the tumor-node-metastasis(TNM)staging system,which does not account for the molecular heterogeneity of this disease.LATS2,a tumor suppressor gene involved in the Hippo signaling pathway,has been identified as a potential prognostic biomarker in gastric cancer.AIM To construct and validate a nomogram model that includes LATS2 expression to predict the survival prognosis of advanced gastric cancer patients following ra-dical surgery,and compare its predictive performance with traditional TNM staging.METHODS A retrospective analysis of 245 advanced gastric cancer patients from the Fourth Hospital of Hebei Medical University was conducted.The patients were divided into a training group(171 patients)and a validation group(74 patients)to deve-lop and test our prognostic model.The performance of the model was determined using C-indices,receiver operating characteristic curves,calibration plots,and decision curves.RESULTS The model demonstrated a high predictive accuracy with C-indices of 0.829 in the training set and 0.862 in the validation set.Area under the curve values for three-year and five-year survival prediction were significantly robust,suggesting an excellent discrimination ability.Calibration plots confirmed the high concordance between the predictions and actual survival outcomes.CONCLUSION We developed a nomogram model incorporating LATS2 expression,which significantly outperformed conven-tional TNM staging in predicting the prognosis of advanced gastric cancer patients postsurgery.This model may serve as a valuable tool for individualized patient management,allowing for more accurate stratification and im-proved clinical outcomes.Further validation in larger patient cohorts will be necessary to establish its generaliza-bility and clinical utility.展开更多
BACKGROUND Advanced gastric cancer is a common malignancy that is often diagnosed at an advanced stage and is still at risk of recurrence after radical surgical treatment.Chemoradiotherapy,as one of the important trea...BACKGROUND Advanced gastric cancer is a common malignancy that is often diagnosed at an advanced stage and is still at risk of recurrence after radical surgical treatment.Chemoradiotherapy,as one of the important treatment methods for gastric cancer,is of great significance for improving the survival rate of patients.However,the tumor recurrence and survival prognosis of gastric cancer patients after radio-therapy and chemotherapy are still uncertain.AIM To analyze the tumor recurrence after radical radiotherapy and chemotherapy for advanced gastric cancer and provide more in-depth guidance for clinicians.METHODS A retrospective analysis was performed on 171 patients with gastric cancer who received postoperative adjuvant radiotherapy and chemotherapy in our hospital from 2021 to 2023.The Kaplan-Meier method was used to calculate the recurrence rate and survival rate;the log-rank method was used to analyze the single-factor prognosis;and the Cox model was used to analyze the prognosis associated with multiple factors.RESULTS The median follow-up time of the whole group was 63 months,and the follow-up rate was 93.6%.Stage Ⅱ and Ⅲ patients accounted for 31.0%and 66.7%,respec-tively.The incidences of Grade 3 and above acute gastrointestinal reactions and hematological adverse reactions were 8.8%and 9.9%,respectively.A total of 166 patients completed the entire chemoradiotherapy regimen,during which no adverse reaction-related deaths occurred.In terms of the recurrence pattern,17 patients had local recurrence,29 patients had distant metastasis,and 12 patients had peritoneal implantation metastasis.The 1-year,3-year,and 5-year overall survival(OS)rates were 83.7%,66.3%,and 60.0%,respectively.The 1-year,3-year,and 5-year disease-free survival rates were 75.5%,62.7%,and 56.5%,respectively.Multivariate analysis revealed that T stage,peripheral nerve invasion,and the lymph node metastasis rate(LNR)were independent prognostic factors for OS.CONCLUSION Postoperative intensity-modulated radiotherapy combined with chemotherapy for gastric cancer treatment is well tolerated and has acceptable adverse effects,which is beneficial for local tumor control and can improve the long-term survival of patients.The LNR was an independent prognostic factor for OS.For patients with a high risk of local recurrence,postoperative adjuvant chemoradiation should be considered.展开更多
BACKGROUND Gastric cancer(GC)is a common malignancy of the digestive system.According to global 2018 cancer data,GC has the fifth-highest incidence and the thirdhighest fatality rate among malignant tumors.More than 6...BACKGROUND Gastric cancer(GC)is a common malignancy of the digestive system.According to global 2018 cancer data,GC has the fifth-highest incidence and the thirdhighest fatality rate among malignant tumors.More than 60%of GC are linked to infection with Helicobacter pylori(H.pylori),a gram-negative,active,microaerophilic,and helical bacterium.This parasite induces GC by producing toxic factors,such as cytotoxin-related gene A,vacuolar cytotoxin A,and outer membrane proteins.Ferroptosis,or iron-dependent programmed cell death,has been linked to GC,although there has been little research on the link between H.pylori infection-related GC and ferroptosis.AIM To identify coregulated differentially expressed genes among ferroptosis-related genes(FRGs)in GC patients and develop a ferroptosis-related prognostic model with discrimination ability.METHODS Gene expression profiles of GC patients and those with H.pylori-associated GC were obtained from The Cancer Genome Atlas and Gene Expression Omnibus(GEO)databases.The FRGs were acquired from the FerrDb database.A ferroptosis-related gene prognostic index(FRGPI)was created using least absolute shrinkage and selection operator–Cox regression.The predictive ability of the FRGPI was validated in the GEO cohort.Finally,we verified the expression of the hub genes and the activity of the ferroptosis inducer FIN56 in GC cell lines and tissues.RESULTS Four hub genes were identified(NOX4,MTCH1,GABARAPL2,and SLC2A3)and shown to accurately predict GC and H.pylori-associated GC.The FRGPI based on the hub genes could independently predict GC patient survival;GC patients in the high-risk group had considerably worse overall survival than did those in the low-risk group.The FRGPI was a significant predictor of GC prognosis and was strongly correlated with disease progression.Moreover,the gene expression levels of common immune checkpoint proteins dramatically increased in the highrisk subgroup of the FRGPI cohort.The hub genes were also confirmed to be highly overexpressed in GC cell lines and tissues and were found to be primarily localized at the cell membrane.The ferroptosis inducer FIN56 inhibited GC cell proliferation in a dose-dependent manner.CONCLUSION In this study,we developed a predictive model based on four FRGs that can accurately predict the prognosis of GC patients and the efficacy of immunotherapy in this population.展开更多
BACKGROUND Gastric cancer(GC)is a highly aggressive malignancy with a heterogeneous nature,which makes prognosis prediction and treatment determination difficult.Inflammation is now recognized as one of the hallmarks ...BACKGROUND Gastric cancer(GC)is a highly aggressive malignancy with a heterogeneous nature,which makes prognosis prediction and treatment determination difficult.Inflammation is now recognized as one of the hallmarks of cancer and plays an important role in the aetiology and continued growth of tumours.Inflammation also affects the prognosis of GC patients.Recent reports suggest that a number of inflammatory-related biomarkers are useful for predicting tumour prognosis.However,the importance of inflammatory-related biomarkers in predicting the prognosis of GC patients is still unclear.AIM To investigate inflammatory-related biomarkers in predicting the prognosis of GC patients.was constructed using the least absolute shrinkage and selection operator Cox regression model based on the GEO database.GC patients from the GSE26253 cohort were used for validation.Univariate and multivariate Cox analyses were used to determine the independent prognostic factors,and a prognostic nomogram was established.The calibration curve and the area under the curve based on receiver operating characteristic analysis were utilized to evaluate the predictive value of the nomogram.The decision curve analysis results were plotted to quantify and assess the clinical value of the nomogram.Gene set enrichment analysis was performed to explore the potential regulatory pathways involved.The relationship between tumour immune infiltration status and risk score was analysed via Tumour Immune Estimation Resource and CIBERSORT.Finally,we analysed the association between risk score and patient sensitivity to commonly used chemotherapy and targeted therapy agents.RESULTS A prognostic model consisting of three inflammatory-related genes(MRPS17,GUF1,and PDK4)was constructed.Independent prognostic analysis revealed that the risk score was a separate prognostic factor in GC patients.According to the risk score,GC patients were stratified into high-and low-risk groups,and patients in the high-risk group had significantly worse prognoses according to age,sex,TNM stage and Lauren type.Consensus clustering identified three subtypes of inflammation that could predict GC prognosis more accurately than traditional grading and staging.Finally,the study revealed that patients in the low-risk group were more sensitive to certain drugs than were those in the high-risk group,indicating a link between inflammation-related genes and drug sensitivity.CONCLUSION In conclusion,we established a novel three-gene prognostic signature that may be useful for predicting the prognosis and personalizing treatment decisions of GC patients.展开更多
BACKGROUND Gastric cancer has a high incidence and fatality rate,and surgery is the preferred course of treatment.Nonetheless,patient survival rates are still low,and the incidence of major postoperative complications...BACKGROUND Gastric cancer has a high incidence and fatality rate,and surgery is the preferred course of treatment.Nonetheless,patient survival rates are still low,and the incidence of major postoperative complications cannot be disregarded.The systemic inflammatory response,nutritional level,and coagulation status are key factors affecting the postoperative recovery and prognosis of gastric cancer patients.The systemic inflammatory response index(SIRI)and the albumin fibrinogen ratio(AFR)are two valuable comprehensive indicators of the severity and prognosis of systemic inflammation in various medical conditions.AIM To assess the clinical importance and prognostic significance of the SIRI scores and the AFR on early postoperative outcomes in patients undergoing radical gastric cancer surgery.METHODS We conducted a retrospective analysis of the clinicopathological characteristics and relevant laboratory indices of 568 gastric cancer patients from January 2018 to December 2019.We calculated and compared two indicators of inflammation and then examined the diagnostic ability of combined SIRI and AFR values for serious early postoperative complications.We scored the patients and categorized them into three groups based on their SIRI and AFR levels.COX analysis was used to compare the three groups of patients the prognostic value of various preoperative SIRI-AFR scores for 5-year overall survival(OS)and disease-free survival(DFS).RESULTS SIRI-AFR scores were an independent risk factor for prognosis[OS:P=0.004;hazards ratio(HR)=3.134;DFS:P<0.001;HR=3.543]and had the highest diagnostic power(area under the curve:0.779;95%confidence interval:0.737-0.820)for early serious complications in patients with gastric cancer.The tumor-node-metastasis stage(P=0.001),perioperative transfusion(P=0.044),positive carcinoembryonic antigen(P=0.014)findings,and major postoperative complications(P=0.011)were factors associated with prognosis.CONCLUSION Preoperative SIRI and AFR values were significantly associated with early postoperative survival and the occurrence of severe complications in gastric cancer patients.展开更多
BACKGROUND Gastric cancer(GC)has a high mortality rate worldwide.Despite significant progress in GC diagnosis and treatment,the prognosis for affected patients still remains unfavorable.AIM To identify important candi...BACKGROUND Gastric cancer(GC)has a high mortality rate worldwide.Despite significant progress in GC diagnosis and treatment,the prognosis for affected patients still remains unfavorable.AIM To identify important candidate genes related to the development of GC and iden-tify potential pathogenic mechanisms through comprehensive bioinformatics analysis.METHODS The Gene Expression Omnibus database was used to obtain the GSE183136 dataset,which includes a total of 135 GC samples.The limma package in R software was employed to identify differentially expressed genes(DEGs).Thereafter,enrichment analyses of Gene Ontology(GO)terms and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways were performed for the gene modules using the clusterProfile package in R software.The protein-protein interaction(PPI)networks of target genes were constructed using STRING and visualized by Cytoscape software.The common hub genes that emerged in the cohort of DEGs that was retrieved from the GEPIA database were then screened using a Venn Diagram.The expression levels of these overlapping genes in stomach adenocarcinoma samples and non-tumor samples and their association with prognosis in GC patients were also obtained from the GEPIA database and Kaplan-Meier curves.Moreover,real-time quantitative polymerase chain reaction(RT-qPCR)and western blotting were performed to determine the mRNA and protein levels of glutamic-pyruvic transaminase(GPT)in GC and normal immortalized cell lines.In addition,cell viability,cell cycle distribution,migration and invasion were evaluated by cell counting kit-8,flow cytometry and transwell assays.Furthermore,we also conducted a retrospective analysis on 70 GC patients diagnosed and surgically treated in Wenzhou Central Hospital,Dingli Clinical College of Wenzhou Medical University,The Second Affiliated Hospital of Shanghai University between January 2017 to December 2020.The tumor and adjacent normal samples were collected from the patients to determine the potential association between the expression level of GPT and the clinical as well as pathological features of GC patients.RESULTS We selected 19214 genes from the GSE183136 dataset,among which there were 250 downregulated genes and 401 upregulated genes in the tumor samples of stage III-IV in comparison to those in tumor samples of stage I-II with a P-value<0.05.In addition,GO and KEGG results revealed that the various upregulated DEGs were mainly enriched in plasma membrane and neuroactive ligand-receptor interaction,whereas the downregulated DEGs were primarily enriched in cytosol and pancreatic secretion,vascular smooth muscle contraction and biosynthesis of the different cofactors.Furthermore,PPI networks were constructed based on the various upregulated and downregulated genes,and there were a total 15 upregulated and 10 downregulated hub genes.After a comprehensive analysis,several hub genes,including runt-related transcription factor 2(RUNX2),salmonella pathogenicity island 1(SPI1),lysyl oxidase(LOX),fibrillin 1(FBN1)and GPT,displayed prognostic values.Interestingly,it was observed that GPT was downregulated in GC cells and its upregulation could suppress the malignant phenotypes of GC cells.Furthermore,the expression level of GPT was found to be associated with age,lymph node metastasis,pathological staging and distant metastasis(P<0.05).CONCLUSION RUNX2,SPI1,LOX,FBN1 and GPT were identified key hub genes in GC by bioinformatics analysis.GPT was significantly associated with the prognosis of GC,and its upregulation can effectively inhibit the proliferative,migrative and invasive capabilities of GC cells.展开更多
BACKGROUND Inflammation-related markers including neutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio(PLR),monocyte-to-lymphocyte ratio(MLR),systemic immune-inflammation index(SII),systemic inflammation r...BACKGROUND Inflammation-related markers including neutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio(PLR),monocyte-to-lymphocyte ratio(MLR),systemic immune-inflammation index(SII),systemic inflammation response index(SIRI)and prognostic nutritional index(PNI)could reflect tumor immune microenvironment and predict prognosis of cancers.However,it had not been explored in alpha-fetoprotein(AFP)producing gastric cancer(GC).AIM To determine the predictive value of inflammation-related peripheral blood markers including as NLR,PLR,MLR,SII,SIRI and PNI in the prognosis of AFPproducing GC(AFPGC).Besides,this study would also compare the differences in tumor immune microenvironment,clinical characteristics and prognosis between AFPGC and AFP-GC patients to improve the understanding of this disease.METHODS 573 patients enrolled were retrospectively studied.They were divided into AFP+group(AFP≥20 ng/mL)and AFP-group(AFP<20 ng/mL),comparing the levels of NLR/PLR/MLR/SII/SIRI/PNI and prognosis.In AFP+group,the impact of NLR/PLR/MLR/SII/SIRI/PNI and their dynamic changes on prognosis were further explored.RESULTS Compared with AFP-patients,AFP+patients had higher NLR/PLR/MLR/SII/-SIRI and lower PNI levels and poorer overall survival(OS).In the AFP+group,mortality was significantly lower in the lower NLR/PLR/MLR/SII/SIRI group and higher PNI group.Moreover,the dynamic increase(NLR/PLR/MLR/SII/-SIRI)or decrease(PNI)was associated with the rise of mortality within 1 year of follow-up.CONCLUSION Compared with AFP-patients,the level of inflammation-related peripheral blood markers significantly increased in AFP+patients,which was correlated with OS of AFP+patients.Also,the gradual increase of SII and SIRI was associated with the risk of death within one year in AFP+patients.AFPGC should be considered as a separate type and distinguished from AFP-GC because of the difference in tumor immune microenvironment.It requires basic experiments and large clinical samples in the future.展开更多
BACKGROUND The systemic inflammatory response index(SIRI)has been demonstrated to make a significant difference in assessing the prognosis of patients with different solid neoplasms.However,research is needed to ascer...BACKGROUND The systemic inflammatory response index(SIRI)has been demonstrated to make a significant difference in assessing the prognosis of patients with different solid neoplasms.However,research is needed to ascertain the accuracy and reliability of applying the SIRI to patients who undergo robotic radical gastric cancer sur-gery.AIM To validate the applicability of the SIRI in assessing the survival of gastric cancer patients and evaluate the clinical contribution of preoperative SIRI levels to predicting long-term tumor outcomes in patients,who received robotic radical gastric cancer surgery.METHODS Initially,an exhaustive retrieval was performed in the PubMed,the Cochrane Library,EMBASE,Web of Science,and Scopus databases to identify relevant studies.Subsequently,a meta-analysis was executed on 6 cohort studies iden-tifying the value of the SIRI in assessing the survival of gastric cancer patients.Additionally,the clinical data of 161 patients undergoing robotic radical gastric cancer surgery were retrospectively analyzed to evaluate their clinicopathological characteristics and relevant laboratory indicators.The association between preoperative SIRI levels and 5-year overall survival(OS)and disease-free survival(DFS)was assessed.RESULTS The findings demonstrated an extensive connection between SIRI values and the outcome of patients with gastric cancer.Preoperative SIRI levels were identified as an independent hazard feature for both OS and DFS among those who received robotic surgery for gastric cancer.SIRI levels in gastric cancer patients were observed to be associated with the presence of comorbidities,T-stage,carcinoembryonic antigen levels,the development of early serious postoperative complications,and the rate of lymph node metastasis.CONCLUSION SIRI values are correlated with adverse in the gastric cancer population and have the potential to be utilized in predicting long-term oncological survival in patients who undergo robotic radical gastric cancer surgery.展开更多
BACKGROUND Although immune checkpoint inhibitors(ICIs)have demonstrated significant survival benefits in some patients diagnosed with gastric cancer(GC),existing prognostic markers are not universally applicable to al...BACKGROUND Although immune checkpoint inhibitors(ICIs)have demonstrated significant survival benefits in some patients diagnosed with gastric cancer(GC),existing prognostic markers are not universally applicable to all patients with advanced GC.AIM To investigate biomarkers that predict prognosis in GC patients treated with ICIs and develop accurate predictive models.METHODS Data from 273 patients diagnosed with GC and distant metastasis,who un-derwent≥1 cycle(s)of ICIs therapy were included in this study.Patients were randomly divided into training and test sets at a ratio of 7:3.Training set data were used to develop the machine learning models,and the test set was used to validate their predictive ability.Shapley additive explanations were used to provide insights into the best model.RESULTS Among the 273 patients with GC treated with ICIs in this study,112 died within 1 year,and 129 progressed within the same timeframe.Five features related to overall survival and 4 related to progression-free survival were identified and used to construct eXtreme Gradient Boosting(XGBoost),logistic regression,and decision tree.After comprehensive evaluation,XGBoost demonstrated good accuracy in predicting overall survival and progression-free survival.CONCLUSION The XGBoost model aided in identifying patients with GC who were more likely to benefit from ICIs therapy.Patient nutritional status may,to some extent,reflect prognosis.展开更多
BACKGROUND Gastric cancer is a kind of malignant tumor which is prevalent all over the world.Although some progress has been made in the treatment of gastric cancer,its prognosis is still not optimistic,so it is of gr...BACKGROUND Gastric cancer is a kind of malignant tumor which is prevalent all over the world.Although some progress has been made in the treatment of gastric cancer,its prognosis is still not optimistic,so it is of great significance to find reliable prog-nostic indicators to guide the treatment and management of patients with gastric cancer.AIM To explore the relationship between serum levels of five biomarkers[carcinoem-bryonic antigen(CEA),carbohydrate antigen(CA)19-9,CA72-4,CA24-2,and ferritin]and prognosis in patients with gastric cancer.METHODS This study included 200 patients with gastric adenocarcinoma,and conducted an in-depth analysis of their baseline characteristics,relationship between tumor markers and staging,and prognosis.The study found that CA19-9 has a signi-ficant correlation with tumor stage,the average levels of CA24-2,CEA,CA72-4 and ferritin were slightly increased disregarding the stage of tumor.Survival analysis showed that increases in CEA,CA19-9,CA24-2,and ferritin were all associated with shortened overall survival of patients.Further multivariate ana-lysis revealed that elevated serum CA72-4 levels were an inde-pendent adverse prognostic factor.RESULTS This study reveals that there is a significant correlation between the expression levels of serum tumor markers CEA,CA19-9,CA72-4,CA24-2 and ferritin in patients with gastric cancer and prognosis,and can be used as important indicators for prognostic evaluation of gastric cancer.In particular,markers that appear abnormally elevated initially may help identify gastric cancer patients with poor prognosis.CONCLUSION Serum CEA and CA19-9 play an important role in the prognosis assessment of gastric cancer,and are effective tools to guide clinical practice and optimize individualized treatment strategies for gastric cancer patients.展开更多
Objective:Accurate prognosis prediction is critical for individualized-therapy making of gastric cancer patients.We aimed to develop and test 6-month,1-,2-,3-,5-,and 10-year overall survival(OS)and cancer-specific sur...Objective:Accurate prognosis prediction is critical for individualized-therapy making of gastric cancer patients.We aimed to develop and test 6-month,1-,2-,3-,5-,and 10-year overall survival(OS)and cancer-specific survival(CSS)prediction models for gastric cancer patients following gastrectomy.Methods:We derived and tested Survival Quilts,a machine learning-based model,to develop 6-month,1-,2-,3-,5-,and 10-year OS and CSS prediction models.Gastrectomy patients in the development set(n=20,583)and the internal validation set(n=5,106)were recruited from the Surveillance,Epidemiology,and End Re-sults(SEER)database,while those in the external validation set(n=6,352)were recruited from the China National Cancer Center Gastric Cancer(NCCGC)database.Furthermore,we selected gastrectomy patients with-out neoadjuvant therapy as a subgroup to train and test the prognostic models in order to keep the accuracy of tumor-node-metastasis(TNM)stage.Prognostic performances of these OS and CSS models were assessed using the Concordance Index(C-index)and area under the curve(AUC)values.Results:The machine learning model had a consistently high accuracy in predicting 6-month,1-,2-,3-,5-,and 10-year OS in the SEER development set(C-index=0.861,0.832,0.789,0.766,0.740,and 0.709;AUC=0.784,0.828,0.840,0.849,0.869,and 0.902,respectively),SEER validation set(C-index=0.782,0.739,0.712,0.698,0.681,and 0.660;AUC=0.751,0.772,0.767,0.762,0.766,and 0.787,respectively),and NCCGC set(C-index=0.691,0.756,0.751,0.737,0.722,and 0.701;AUC=0.769,0.788,0.790,0.790,0.787,and 0.788,respectively).The model was able to predict 6-month,1-,2-,3-,5-,and 10-year CSS in the SEER development set(C-index=0.879,0.858,0.820,0.802,0.784,and 0.774;AUC=0.756,0.827,0.852,0.863,0.874,and 0.884,respectively)and SEER validation set(C-index=0.790,0.763,0.741,0.729,0.718,and 0.708;AUC=0.706,0.758,0.767,0.766,0.766,and 0.764,respectively).In multivariate analysis,the high-risk group with risk score output by 5-year OS model was proved to be a strong survival predictor both in the SEER development set(hazard ratio[HR]=14.59,95%confidence interval[CI]:1.872-2.774,P<0.001),SEER validation set(HR=2.28,95%CI:13.089-16.293,P<0.001),and NCCGC set(HR=1.98,95%CI:1.617-2.437,P<0.001).We further explored the prognostic value of risk score resulted 5-year CSS model of gastrectomy patients,and found that high-risk group remained as an independent CSS factor in the SEER development set(HR=12.81,95%CI:11.568-14.194,P<0.001)and SEER validation set(HR=1.61,95%CI:1.338-1.935,P<0.001).Conclusion:Survival Quilts could allow accurate prediction of 6-month,1-,2-,3-,5-,and 10-year OS and CSS in gastric cancer patients following gastrectomy.展开更多
Nicotinamide adenine dinucleotide(NAD+)plays an essential role in cellular metabolism,mitochondrial homeostasis,inflammation,and senescence.However,the role of NAD+-regulated genes,including coding and long non-coding...Nicotinamide adenine dinucleotide(NAD+)plays an essential role in cellular metabolism,mitochondrial homeostasis,inflammation,and senescence.However,the role of NAD+-regulated genes,including coding and long non-coding genes in cancer development is poorly understood.We constructed a prediction model based on the expression level of NAD+metabolism-related genes(NMRGs).Furthermore,we validated the expression of NMRGs in gastric cancer(GC)tissues and cell lines;additionally,β-nicotinamide mononucleotide(NMN),a precursor of NAD+,was used to treat the GC cell lines to analyze its effects on the expression level of NMRGs lncRNAs and cellular proliferation,cell cycle,apoptosis,and senescence-associated secretory phenotype(SASP).A total of 13 NMRGs-related lncRNAs were selected to construct prognostic risk signatures,and patients with high-risk scores had a poor prognosis.Some immune checkpoint genes were upregulated in the high-risk group.In addition,cell cycle,epigenetics,and senescence were significantly downregulated in the high-risk group.Notably,we found that the levels of immune cell infiltration,including CD8 T cells,CD4 naïve T cells,CD4 memory-activated T cells,B memory cells,and naïve B cells,were significantly associated with risk scores.Furthermore,the treatment of NMN showed increased proliferation of AGS and MKN45 cells.In addition,the expression of SASP factors(IL6,IL8,IL10,TGF-β,and TNF-α)was significantly decreased after NMN treatment.We conclude that the lncRNAs associated with NAD+metabolism can potentially be used as biomarkers for predicting clinical outcomes of GC patients.展开更多
BACKGROUND Early gastric cancer(EGC)is a common malignant tumor of the digestive system,and its lymph node metastasis and survival prognosis have been concerning.By retrospectively analyzing the clinical data of EGC p...BACKGROUND Early gastric cancer(EGC)is a common malignant tumor of the digestive system,and its lymph node metastasis and survival prognosis have been concerning.By retrospectively analyzing the clinical data of EGC patients,we can better under-stand the status of lymph node metastasis and its impact on survival and prog-nosis.AIM To evaluate the prognosis of EGC patients and the factors that affect lymph node METHODS The clinicopathological data of 1011 patients with EGC admitted to our hospital between January 2015 and December 2023 were collected in a retrospective cohort study.There were 561 males and 450 females.The mean age was 58±11 years.The patient underwent radical gastrectomy.The status of lymph node metastasis in each group was determined according to the pathological examination results of surgical specimens.The outcomes were as follows:(1)Lymph node metastasis in EGC patients;(2)Analysis of influencing factors of lymph node metastasis in EGC;and(3)Analysis of prognostic factors in patients with EGC.Normally distributed measurement data are expressed as mean±SD,and a t test was used for comparisons between groups.The data are expressed as absolute numbers or percentages,and the chi-square test was used for comparisons between groups.Rank data were compared using a nonparametric rank sum test.A log-rank test and a logistic regression model were used for univariate analysis.A logistic stepwise regression model and a Cox stepwise regression model were used for multivariate analysis.The Kaplan-Meier method was used to calculate the survival rate and construct survival curves.A log-rank test was used for survival analysis.RESULTS Analysis of influencing factors of lymph node metastasis in EGC.The results of the multifactor analysis showed that tumor length and diameter,tumor site,tumor invasion depth,vascular thrombus,and tumor differentiation degree were independent influencing factors for lymph node metastasis in patients with EGC(odds ratios=1.80,1.49,2.65,5.76,and 0.60;95%CI:1.29–2.50,1.11–2.00,1.81–3.88,3.87-8.59,and 0.48-0.76,respectively;P<0.05).Analysis of prognostic factors in patients with EGC.All 1011 patients with EGC were followed up for 43(0–13)months.The 3-year overall survival rate was 97.32%.Multivariate analysis revealed that age>60 years and lymph node metastasis were independent risk factors for prognosis in patients with EGC(hazard ratio=9.50,2.20;95%CI:3.31-27.29,1.00-4.87;P<0.05).Further analysis revealed that the 3-year overall survival rates of gastric cancer patients aged>60 years and≤60 years were 99.37%and 94.66%,respectively,and the difference was statistically significant(P<0.05).The 3-year overall survival rates of patients with and without lymph node metastasis were 95.42%and 97.92%,respectively,and the difference was statistically significant(P<0.05).CONCLUSION The lymph node metastasis rate of EGC patients was 23.64%.Tumor length,tumor site,tumor infiltration depth,vascular cancer thrombin,and tumor differentiation degree were found to be independent factors affecting lymph node metastasis in EGC patients.Age>60 years and lymph node metastasis are independent risk factors for EGC prognosis.展开更多
BACKGROUND The hemoglobin,albumin,lymphocyte,and platelet(HALP)score,derived from a composite evaluation of markers reflecting the tumor-inflammation relationship and nutritional status,has been substantiated as a not...BACKGROUND The hemoglobin,albumin,lymphocyte,and platelet(HALP)score,derived from a composite evaluation of markers reflecting the tumor-inflammation relationship and nutritional status,has been substantiated as a noteworthy prognostic determinant for diverse malignancies.AIM To investigate how the HALP score relates to prognosis in patients with metastatic gastric cancer.METHODS The cutoff values for the HALP score,neutrophil/lymphocyte ratio,and platelet/lymphocyte ratio were determined using receiver operating characteristic analysis.Low HALP scores were defined as those less than 24.79 and high HALP scores as those greater than 24.79.RESULTS The study cohort comprised 147 patients and 110 of them(74.8%)were male.The patients'median age was 63(22-89)years.The median overall survival was significantly superior in the patients with high HALP scores than in those with low HALP scores(10.4 mo vs 7.5 mo,respectively;P<0.001)CONCLUSION The HALP score was found to be a prognostic factor in patients with metastatic gastric cancer.展开更多
BACKGROUND Gastric cancer(GC)is a common malignant tumor of the digestive system with a high degree of malignancy.It usually develops insidiously without any specific symptoms in the early stages.As one of the disease...BACKGROUND Gastric cancer(GC)is a common malignant tumor of the digestive system with a high degree of malignancy.It usually develops insidiously without any specific symptoms in the early stages.As one of the diseases caused by abnormal gene changes,GC has abnormal expression of various oncogenes and products during its development.Tumor markers such as carcinoembryonic antigen(CEA),carbohydrate antigen 199(CA199)and carbohydrate antigen 724(CA724)are not expressed or lowly expressed in normal people,but significantly increased after carcinogenesis.Monitoring the changes in the levels of tumor markers such as CEA,CA199 and CA724 is conducive to early diagnosis and evaluation of the occurrence of some solid tumors.AIM To investigate the expression of CEA,CA199 and CA724 in GC and their correlation with clinical features,hoping to provide more effective markers for the early preventive diagnosis of GC.METHODS Of 87 patients with GC admitted to our hospital from September 2020 to December 2021 were included in the GC group,and another 80 healthy people who came to our hospital for physical examination with normal results during the same period were selected as the control group.The serum CEA,CA199,and CA724 levels were compared between the two groups,and the serum CEA,CA199,and CA724 levels were compared in patients with GC at different TNM stages,and the differences in the positive rates of CEA,CA199,and CA724 alone and in combination in detecting TNM stages of GC and GC were compared.In addition,the relationship between the levels of tumor markers CEA,CA199 and CA724 and the clinicopathological characteristics of GC patients was also analyzed.The relationship between the serum levels of CEA,CA199 and CA724 and the survival period of GC patients was analyzed by Pearson.RESULTS The serum levels of CEA,CA199 and CA724 in GC group were significantly higher than those in control group(P<0.05).With the increase of TNM stage,the serum CEA,CA199 and CA724 expression levels in GC patients increased significantly,and the differences between groups were statistically significant(P<0.05).The positive rate of the CA724 single test was higher than that of CEA and CA199 single test(P<0.05).The positive rate of the three combined tests was 95.40%(83/87),which was higher than that of CEA,CA199 and CA724 single tests.The difference was statistically significant(P<0.05).The combined detection positive rates of CEA,CA199,and CA724 in stages I,II,III,and IV of GC were 89.66%,93.10%,98.85%,and 100.00%respectively,all of which were higher than the individual detection rates of CEA,CA199,and CA724.The differences were statistically significant(P<0.05).There was no significant difference in serum CEA,CA199 and CA724 levels between GC patients with different genders,smoking history and alcohol history(P>0.05).However,the serum CEA,CA199 and CA724 levels were significantly higher in GC patients aged≥45 years,TNM stage III-IV,with lymph node metastasis and tumor diameter≥5 cm than in GC patients aged<45 years,TNM stage I-II,without lymph node metastasis and tumor diameter<5 cm(P<0.05).CONCLUSION The expression levels of serum tumor markers CEA,CA199 and CA724 in patients with GC are high and rise with the increase of TNM stage.The levels of CEA,CA199 and CA724 are related to age,TNM stage,lymph node metastasis and tumor diameter.The combined detection of CEA,CA199 and CA724 is helpful to improve the diagnostic accuracy of GC with high clinical guidance value.展开更多
BACKGROUND Gastric cancer(GC)is a common malignant tumor of the digestive system.Disulfidptosis is a new programmed cell death mechanism,although its specific mechanism in GC is incompletely understood.AIM In this stu...BACKGROUND Gastric cancer(GC)is a common malignant tumor of the digestive system.Disulfidptosis is a new programmed cell death mechanism,although its specific mechanism in GC is incompletely understood.AIM In this study,we used bioinformatics analysis to explore a disulfidptosis-based predictive model related to GC prognosis and to identify potential therapeutic targets and sensitive drugs for GC.METHODS We extracted GC-related data from The Cancer Genome Atlas and Gene Expression Omnibus databases.R software(version 4.2.1)was used for correlation analysis.RESULTS Through the above analysis,we found that the disulfidptosis related gene may be related to the prognosis of GC.Six genes,namely,PLS3,GRP,APOD,SGCE,COL8A1,and VAMP7,were found to constitute a predictive model for GC prognosis.APOD is a potential therapeutic target for treating GC.Bosutinib and other drugs are sensitive for the treatment of GC.CONCLUSION The results of this study indicate that disulfidptosis is related to the prognosis and treatment of GC,while APOD represents a potential therapeutic target for GC.展开更多
Aim:Scavenger receptor class B,type I(SR-BI)is an integral plasma membrane protein that has been reported to be overexpressed in various malignancies,such as renal cancer,breast cancer,and prostate cancer,and is an in...Aim:Scavenger receptor class B,type I(SR-BI)is an integral plasma membrane protein that has been reported to be overexpressed in various malignancies,such as renal cancer,breast cancer,and prostate cancer,and is an independent prognostic factor.However,the clinical value and expression of SR-BI in GC are unknown.Our research aimed to explore the role of SR-BI in combination with immune markers as a diagnostic and prognostic marker for gastric cancer(GC).Methods:GC tissues,paracancerous tissues,and clinicopathological data of 149 patients were collected.The expression level of SR-BI,Tumor-infiltrating lymphocytes(TILs),and PD-L1 were evaluated by immunohistochemistry(IHC).The associations of the SR-BI staining intensity with clinicopathological features and immune markers were determined by the chi-square test.Univariate and multivariate COX regression analyses were used to evaluate independent prognostic factors.Kaplan–Meier analyses were performed to plot the survival curve.Results:Our results indicated that SR-BI was expressed at higher levels in tumor tissues than in adjacent paracancerous tissues(p<0.001),and patients with high levels of SR-BI expression had a worse prognosis.Univariate and multivariate analyses revealed that high SR-BI expression was an independent factor for poor prognosis.The chi-square test determined that the expression of SR-BI was negatively correlated with CD4+T cells and CD8+T cells(CD4+T cells,p=0.013;CD8+T cells,p=0.021),and positively correlated with PD-L1(p=0.022).Finally,survival analysis revealed that CD4+T cells were associated with the prognosis of GC patients(p=0.019),and the combined survival analysis of SR-BI and CD4+T cells was also statistically significant(p=0.030).Conclusion:SR-BI is highly expressed in GC tissue and associated with poor prognosis.Moreover,SR-BI can also regulate the GC tumor immune microenvironment.展开更多
BACKGROUND Gastric cancer(GC)is a malignant tumor with high morbidity and mortality.Expression of COL5A2 is significantly elevated in GC.Abnormal expression of noncoding RNAs(ncRNAs)have been found in GC,including mic...BACKGROUND Gastric cancer(GC)is a malignant tumor with high morbidity and mortality.Expression of COL5A2 is significantly elevated in GC.Abnormal expression of noncoding RNAs(ncRNAs)have been found in GC,including microRNA(miRNA)and long noncoding RNA(lncRNA).Competing endogenous RNA network plays an important regulatory role in GC.However,its specific regulatory mechanism has not been elucidated.AIM To gain insight into the ncRNA regulatory mechanism and immune microenvironment related to COL5A2 in GC.METHODS RNA sequencing data and clinical information from The Cancer Genome Atlas data portal were used to analyze the expressions of COL5A2,miRNA and lncRNA related to the prognosis of GC.Cox regression analysis and Kyoto Encyclopedia of Genes and Genomes analysis were performed to assess the risk factors and relevant function of COL5A2.StarBase was used to predict the interaction of miRNA–lncRNA or miRNA–mRNA in GC.The relationship between COL5A2,miR-144-3p and ENTPD1-AS1 were verified by dual luciferase reporter assay.The association of COL5A2 with immune cell infiltration were analyzed using the Tumor Immune Estimation Resource database and single sample gene set enrichment analysis.The expression of COL5A2 and macrophages in paired GC tissues were detected by immunohistochemical staining.RESULTS We verified that the upregulation of COL5A2 expression was associated with the prognosis of GC and was an independent risk factor for GC.miR-144-3p was downregulated and correlated with the prognosis of GC.miR-144-3p regulated the expression of COL5A2 through direct interaction with COL5A2.ENTPD1-AS1 was elevated in GC and competitively bound to miR-144-3p,thus inhibiting the expression of miR-144-3p.ENTPD1-AS1 enhanced the expression of COL5A2 through sponging miR-144-3p.Compared to paired normal tissue,COL5A2 expression was upregulated at the protein level,especially in the middle and late stages of GC.The high expression of COL5A2 was positively linked to macrophage infiltration in GC.CONCLUSION COL5A2 regulated by ENTPD1-AS1–miR-144-3p was associated with poor prognosis and macrophage infiltration in GC.This could be a new biomarker and therapeutic target in GC.展开更多
BACKGROUND The prognostic assessment of patients after surgical resection of gastric cancer(GC)patients is critical.However,the role of the circadian clock gene NPAS2 expression in GC remains unknown.AIM To explore th...BACKGROUND The prognostic assessment of patients after surgical resection of gastric cancer(GC)patients is critical.However,the role of the circadian clock gene NPAS2 expression in GC remains unknown.AIM To explore the relationship between NPAS2 and the survival prognosis of GC patients and clarify its role in evaluating GC prognosis.METHODS The tumor tissues and clinical data of 101 patients with GC were collected retrospectively.Immunohistochemical staining(IHC)was used to detect the expression of NPAS2 protein in GC and adjacent tissues.Univariate and multivariate Cox regression analysis was used to determine the independent prognostic factors of GC,and a nomogram prediction model was established.The receiver operating characteristic(ROC)curve,the ROC area under the curve,the calibration curve,and C-index were used to evaluate the predictive effectiveness of the model.Kaplan Meier analysis was used to compare the risk stratification of subgroups according to the median score in the nomogram model of each patient.RESULTS Microarray IHC analysis showed that the positive rate of NPAS2 protein expression in GC tissues was 65.35%,which was significantly higher than 30.69%in adjacent tissues.The high expression of NPAS2 was correlated with tumor-node-metastasis(TNM)stage(P<0.05),pN stage(P<0.05),metastasis(P<0.05),venous invasion(P<0.05),lymphatic invasion(P<0.05),and lymph node positive(P<0.05)of GC.Kaplan Meier survival analysis showed that the 3-year overall survival(OS)of patients with high NPAS2 expression was significantly shortened(P<0.0001).Univariate and multivariate COX regression analysis showed that TNM stage(P=0.009),metastasis(P=0.009),and NPAS2 expression(P=0.020)were independent prognostic factors of OS in GC patients for 3 years.The nomogram prediction model based on independent prognostic factors has a C-Index of 0.740(95%CI:0.713-0.767).Furthermore,subgroup analysis showed that the 3-year OS time of the high-risk group was significantly lower than that of the low-risk group(P<0.0001).CONCLUSION NPAS2 is highly expressed in GC tissues and is closely related to worse OS in patients.Therefore,the evaluation of NPAS2 expression may be a potential marker for GC prognosis evaluation.Notably,the nomogram model based on NPAS2 can improve the accuracy of GC prognosis prediction and assist clinicians in postoperative patient management and decision-making.展开更多
文摘BACKGROUND Gastric cancer(GC)is one of the most common malignant tumors in the world,and its prognosis is closely related to many factors.In recent years,the incidence of vascular thrombosis in patients with GC has gradually attracted increasing attention,and studies have shown that it may have a significant impact on the survival rate and prognosis of patients.However,the specific mechanism underlying the association between vascular thrombosis and the prognosis of patients with GC remains unclear.AIM To analyze the relationships between vascular cancer support and other clinicopathological factors and their influence on the prognosis of patients with GC.METHODS This study retrospectively analyzed the clinicopathological data of 621 patients with GC and divided them into a positive group and a negative group according to the presence or absence of a vascular thrombus.The difference in the 5-year cumulative survival rate between the two groups was compared,and the relationships between vascular cancer thrombus and other clinicopathological factors and their influence on the prognosis of patients with GC were analyzed.RESULTS Among 621 patients with GC,the incidence of vascular thrombi was 31.7%(197 patients).Binary logistic regression analysis revealed that the degree of tumor differentiation,depth of invasion,and extent of lymph node metastasis were independent influencing factors for the occurrence of vascular thrombi in GC patients(P<0.01).The trend of the χ^(2) test showed that the degree of differentiation,depth of invasion,and extent of lymph node metastasis were linearly correlated with the percentage of vascular thrombi in GC patients(P<0.01),and the correlation between lymph node metastasis and vascular thrombi was more significant(r=0.387).Univariate analysis revealed that the 5-year cumulative survival rate of the positive group was significantly lower than that of the negative group(46.7%vs 73.3%,P<0.01).Multivariate analysis revealed that age,tumor diameter,TNM stage,and vascular thrombus were independent risk factors for the prognosis of GC patients(all P<0.05).Further stratified analysis revealed that the 5-year cumulative survival rate of stage Ⅲ GC patients in the thrombolase-positive group was significantly lower than that in the thrombolase-negative group(36.1%vs 51.4%;P<0.05).CONCLUSION Vascular cancer status is an independent risk factor affecting the prognosis of patients with GC.The combination of vascular cancer suppositories and TNM staging can better judge the prognosis of patients with GC and guide more reasonable treatment.
文摘BACKGROUND Gastric cancer is a leading cause of cancer-related deaths worldwide.Prognostic assessments are typically based on the tumor-node-metastasis(TNM)staging system,which does not account for the molecular heterogeneity of this disease.LATS2,a tumor suppressor gene involved in the Hippo signaling pathway,has been identified as a potential prognostic biomarker in gastric cancer.AIM To construct and validate a nomogram model that includes LATS2 expression to predict the survival prognosis of advanced gastric cancer patients following ra-dical surgery,and compare its predictive performance with traditional TNM staging.METHODS A retrospective analysis of 245 advanced gastric cancer patients from the Fourth Hospital of Hebei Medical University was conducted.The patients were divided into a training group(171 patients)and a validation group(74 patients)to deve-lop and test our prognostic model.The performance of the model was determined using C-indices,receiver operating characteristic curves,calibration plots,and decision curves.RESULTS The model demonstrated a high predictive accuracy with C-indices of 0.829 in the training set and 0.862 in the validation set.Area under the curve values for three-year and five-year survival prediction were significantly robust,suggesting an excellent discrimination ability.Calibration plots confirmed the high concordance between the predictions and actual survival outcomes.CONCLUSION We developed a nomogram model incorporating LATS2 expression,which significantly outperformed conven-tional TNM staging in predicting the prognosis of advanced gastric cancer patients postsurgery.This model may serve as a valuable tool for individualized patient management,allowing for more accurate stratification and im-proved clinical outcomes.Further validation in larger patient cohorts will be necessary to establish its generaliza-bility and clinical utility.
基金Supported by the Hebei Provincial Department of Finance and the Hebei Provincial Health Commission,No.ZF2023242。
文摘BACKGROUND Advanced gastric cancer is a common malignancy that is often diagnosed at an advanced stage and is still at risk of recurrence after radical surgical treatment.Chemoradiotherapy,as one of the important treatment methods for gastric cancer,is of great significance for improving the survival rate of patients.However,the tumor recurrence and survival prognosis of gastric cancer patients after radio-therapy and chemotherapy are still uncertain.AIM To analyze the tumor recurrence after radical radiotherapy and chemotherapy for advanced gastric cancer and provide more in-depth guidance for clinicians.METHODS A retrospective analysis was performed on 171 patients with gastric cancer who received postoperative adjuvant radiotherapy and chemotherapy in our hospital from 2021 to 2023.The Kaplan-Meier method was used to calculate the recurrence rate and survival rate;the log-rank method was used to analyze the single-factor prognosis;and the Cox model was used to analyze the prognosis associated with multiple factors.RESULTS The median follow-up time of the whole group was 63 months,and the follow-up rate was 93.6%.Stage Ⅱ and Ⅲ patients accounted for 31.0%and 66.7%,respec-tively.The incidences of Grade 3 and above acute gastrointestinal reactions and hematological adverse reactions were 8.8%and 9.9%,respectively.A total of 166 patients completed the entire chemoradiotherapy regimen,during which no adverse reaction-related deaths occurred.In terms of the recurrence pattern,17 patients had local recurrence,29 patients had distant metastasis,and 12 patients had peritoneal implantation metastasis.The 1-year,3-year,and 5-year overall survival(OS)rates were 83.7%,66.3%,and 60.0%,respectively.The 1-year,3-year,and 5-year disease-free survival rates were 75.5%,62.7%,and 56.5%,respectively.Multivariate analysis revealed that T stage,peripheral nerve invasion,and the lymph node metastasis rate(LNR)were independent prognostic factors for OS.CONCLUSION Postoperative intensity-modulated radiotherapy combined with chemotherapy for gastric cancer treatment is well tolerated and has acceptable adverse effects,which is beneficial for local tumor control and can improve the long-term survival of patients.The LNR was an independent prognostic factor for OS.For patients with a high risk of local recurrence,postoperative adjuvant chemoradiation should be considered.
文摘BACKGROUND Gastric cancer(GC)is a common malignancy of the digestive system.According to global 2018 cancer data,GC has the fifth-highest incidence and the thirdhighest fatality rate among malignant tumors.More than 60%of GC are linked to infection with Helicobacter pylori(H.pylori),a gram-negative,active,microaerophilic,and helical bacterium.This parasite induces GC by producing toxic factors,such as cytotoxin-related gene A,vacuolar cytotoxin A,and outer membrane proteins.Ferroptosis,or iron-dependent programmed cell death,has been linked to GC,although there has been little research on the link between H.pylori infection-related GC and ferroptosis.AIM To identify coregulated differentially expressed genes among ferroptosis-related genes(FRGs)in GC patients and develop a ferroptosis-related prognostic model with discrimination ability.METHODS Gene expression profiles of GC patients and those with H.pylori-associated GC were obtained from The Cancer Genome Atlas and Gene Expression Omnibus(GEO)databases.The FRGs were acquired from the FerrDb database.A ferroptosis-related gene prognostic index(FRGPI)was created using least absolute shrinkage and selection operator–Cox regression.The predictive ability of the FRGPI was validated in the GEO cohort.Finally,we verified the expression of the hub genes and the activity of the ferroptosis inducer FIN56 in GC cell lines and tissues.RESULTS Four hub genes were identified(NOX4,MTCH1,GABARAPL2,and SLC2A3)and shown to accurately predict GC and H.pylori-associated GC.The FRGPI based on the hub genes could independently predict GC patient survival;GC patients in the high-risk group had considerably worse overall survival than did those in the low-risk group.The FRGPI was a significant predictor of GC prognosis and was strongly correlated with disease progression.Moreover,the gene expression levels of common immune checkpoint proteins dramatically increased in the highrisk subgroup of the FRGPI cohort.The hub genes were also confirmed to be highly overexpressed in GC cell lines and tissues and were found to be primarily localized at the cell membrane.The ferroptosis inducer FIN56 inhibited GC cell proliferation in a dose-dependent manner.CONCLUSION In this study,we developed a predictive model based on four FRGs that can accurately predict the prognosis of GC patients and the efficacy of immunotherapy in this population.
文摘BACKGROUND Gastric cancer(GC)is a highly aggressive malignancy with a heterogeneous nature,which makes prognosis prediction and treatment determination difficult.Inflammation is now recognized as one of the hallmarks of cancer and plays an important role in the aetiology and continued growth of tumours.Inflammation also affects the prognosis of GC patients.Recent reports suggest that a number of inflammatory-related biomarkers are useful for predicting tumour prognosis.However,the importance of inflammatory-related biomarkers in predicting the prognosis of GC patients is still unclear.AIM To investigate inflammatory-related biomarkers in predicting the prognosis of GC patients.was constructed using the least absolute shrinkage and selection operator Cox regression model based on the GEO database.GC patients from the GSE26253 cohort were used for validation.Univariate and multivariate Cox analyses were used to determine the independent prognostic factors,and a prognostic nomogram was established.The calibration curve and the area under the curve based on receiver operating characteristic analysis were utilized to evaluate the predictive value of the nomogram.The decision curve analysis results were plotted to quantify and assess the clinical value of the nomogram.Gene set enrichment analysis was performed to explore the potential regulatory pathways involved.The relationship between tumour immune infiltration status and risk score was analysed via Tumour Immune Estimation Resource and CIBERSORT.Finally,we analysed the association between risk score and patient sensitivity to commonly used chemotherapy and targeted therapy agents.RESULTS A prognostic model consisting of three inflammatory-related genes(MRPS17,GUF1,and PDK4)was constructed.Independent prognostic analysis revealed that the risk score was a separate prognostic factor in GC patients.According to the risk score,GC patients were stratified into high-and low-risk groups,and patients in the high-risk group had significantly worse prognoses according to age,sex,TNM stage and Lauren type.Consensus clustering identified three subtypes of inflammation that could predict GC prognosis more accurately than traditional grading and staging.Finally,the study revealed that patients in the low-risk group were more sensitive to certain drugs than were those in the high-risk group,indicating a link between inflammation-related genes and drug sensitivity.CONCLUSION In conclusion,we established a novel three-gene prognostic signature that may be useful for predicting the prognosis and personalizing treatment decisions of GC patients.
基金the National Natural Science Foundation of China,No.8236110677Central to guide local scientific and Technological Development,No.ZYYDDFFZZJ-1+1 种基金Natural Science Foundation of Gansu Province,China,No.18JR2RA033Gansu Da Vinci Robot High-End Diagnosis and Treatment Team Construction Project,National Key Research and Development Program,No.2020RCXM076.
文摘BACKGROUND Gastric cancer has a high incidence and fatality rate,and surgery is the preferred course of treatment.Nonetheless,patient survival rates are still low,and the incidence of major postoperative complications cannot be disregarded.The systemic inflammatory response,nutritional level,and coagulation status are key factors affecting the postoperative recovery and prognosis of gastric cancer patients.The systemic inflammatory response index(SIRI)and the albumin fibrinogen ratio(AFR)are two valuable comprehensive indicators of the severity and prognosis of systemic inflammation in various medical conditions.AIM To assess the clinical importance and prognostic significance of the SIRI scores and the AFR on early postoperative outcomes in patients undergoing radical gastric cancer surgery.METHODS We conducted a retrospective analysis of the clinicopathological characteristics and relevant laboratory indices of 568 gastric cancer patients from January 2018 to December 2019.We calculated and compared two indicators of inflammation and then examined the diagnostic ability of combined SIRI and AFR values for serious early postoperative complications.We scored the patients and categorized them into three groups based on their SIRI and AFR levels.COX analysis was used to compare the three groups of patients the prognostic value of various preoperative SIRI-AFR scores for 5-year overall survival(OS)and disease-free survival(DFS).RESULTS SIRI-AFR scores were an independent risk factor for prognosis[OS:P=0.004;hazards ratio(HR)=3.134;DFS:P<0.001;HR=3.543]and had the highest diagnostic power(area under the curve:0.779;95%confidence interval:0.737-0.820)for early serious complications in patients with gastric cancer.The tumor-node-metastasis stage(P=0.001),perioperative transfusion(P=0.044),positive carcinoembryonic antigen(P=0.014)findings,and major postoperative complications(P=0.011)were factors associated with prognosis.CONCLUSION Preoperative SIRI and AFR values were significantly associated with early postoperative survival and the occurrence of severe complications in gastric cancer patients.
文摘BACKGROUND Gastric cancer(GC)has a high mortality rate worldwide.Despite significant progress in GC diagnosis and treatment,the prognosis for affected patients still remains unfavorable.AIM To identify important candidate genes related to the development of GC and iden-tify potential pathogenic mechanisms through comprehensive bioinformatics analysis.METHODS The Gene Expression Omnibus database was used to obtain the GSE183136 dataset,which includes a total of 135 GC samples.The limma package in R software was employed to identify differentially expressed genes(DEGs).Thereafter,enrichment analyses of Gene Ontology(GO)terms and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways were performed for the gene modules using the clusterProfile package in R software.The protein-protein interaction(PPI)networks of target genes were constructed using STRING and visualized by Cytoscape software.The common hub genes that emerged in the cohort of DEGs that was retrieved from the GEPIA database were then screened using a Venn Diagram.The expression levels of these overlapping genes in stomach adenocarcinoma samples and non-tumor samples and their association with prognosis in GC patients were also obtained from the GEPIA database and Kaplan-Meier curves.Moreover,real-time quantitative polymerase chain reaction(RT-qPCR)and western blotting were performed to determine the mRNA and protein levels of glutamic-pyruvic transaminase(GPT)in GC and normal immortalized cell lines.In addition,cell viability,cell cycle distribution,migration and invasion were evaluated by cell counting kit-8,flow cytometry and transwell assays.Furthermore,we also conducted a retrospective analysis on 70 GC patients diagnosed and surgically treated in Wenzhou Central Hospital,Dingli Clinical College of Wenzhou Medical University,The Second Affiliated Hospital of Shanghai University between January 2017 to December 2020.The tumor and adjacent normal samples were collected from the patients to determine the potential association between the expression level of GPT and the clinical as well as pathological features of GC patients.RESULTS We selected 19214 genes from the GSE183136 dataset,among which there were 250 downregulated genes and 401 upregulated genes in the tumor samples of stage III-IV in comparison to those in tumor samples of stage I-II with a P-value<0.05.In addition,GO and KEGG results revealed that the various upregulated DEGs were mainly enriched in plasma membrane and neuroactive ligand-receptor interaction,whereas the downregulated DEGs were primarily enriched in cytosol and pancreatic secretion,vascular smooth muscle contraction and biosynthesis of the different cofactors.Furthermore,PPI networks were constructed based on the various upregulated and downregulated genes,and there were a total 15 upregulated and 10 downregulated hub genes.After a comprehensive analysis,several hub genes,including runt-related transcription factor 2(RUNX2),salmonella pathogenicity island 1(SPI1),lysyl oxidase(LOX),fibrillin 1(FBN1)and GPT,displayed prognostic values.Interestingly,it was observed that GPT was downregulated in GC cells and its upregulation could suppress the malignant phenotypes of GC cells.Furthermore,the expression level of GPT was found to be associated with age,lymph node metastasis,pathological staging and distant metastasis(P<0.05).CONCLUSION RUNX2,SPI1,LOX,FBN1 and GPT were identified key hub genes in GC by bioinformatics analysis.GPT was significantly associated with the prognosis of GC,and its upregulation can effectively inhibit the proliferative,migrative and invasive capabilities of GC cells.
文摘BACKGROUND Inflammation-related markers including neutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio(PLR),monocyte-to-lymphocyte ratio(MLR),systemic immune-inflammation index(SII),systemic inflammation response index(SIRI)and prognostic nutritional index(PNI)could reflect tumor immune microenvironment and predict prognosis of cancers.However,it had not been explored in alpha-fetoprotein(AFP)producing gastric cancer(GC).AIM To determine the predictive value of inflammation-related peripheral blood markers including as NLR,PLR,MLR,SII,SIRI and PNI in the prognosis of AFPproducing GC(AFPGC).Besides,this study would also compare the differences in tumor immune microenvironment,clinical characteristics and prognosis between AFPGC and AFP-GC patients to improve the understanding of this disease.METHODS 573 patients enrolled were retrospectively studied.They were divided into AFP+group(AFP≥20 ng/mL)and AFP-group(AFP<20 ng/mL),comparing the levels of NLR/PLR/MLR/SII/SIRI/PNI and prognosis.In AFP+group,the impact of NLR/PLR/MLR/SII/SIRI/PNI and their dynamic changes on prognosis were further explored.RESULTS Compared with AFP-patients,AFP+patients had higher NLR/PLR/MLR/SII/-SIRI and lower PNI levels and poorer overall survival(OS).In the AFP+group,mortality was significantly lower in the lower NLR/PLR/MLR/SII/SIRI group and higher PNI group.Moreover,the dynamic increase(NLR/PLR/MLR/SII/-SIRI)or decrease(PNI)was associated with the rise of mortality within 1 year of follow-up.CONCLUSION Compared with AFP-patients,the level of inflammation-related peripheral blood markers significantly increased in AFP+patients,which was correlated with OS of AFP+patients.Also,the gradual increase of SII and SIRI was associated with the risk of death within one year in AFP+patients.AFPGC should be considered as a separate type and distinguished from AFP-GC because of the difference in tumor immune microenvironment.It requires basic experiments and large clinical samples in the future.
基金Supported by National Natural Science Foundation of China,No.8236110677Natural Science Foundation of Gansu Province,No.18JR2RA033Gansu Da Vinci Robot High-End Diagnosis and Treatment Team Construction Project,National Key Research and Development Program,No.2020RCXM076.
文摘BACKGROUND The systemic inflammatory response index(SIRI)has been demonstrated to make a significant difference in assessing the prognosis of patients with different solid neoplasms.However,research is needed to ascertain the accuracy and reliability of applying the SIRI to patients who undergo robotic radical gastric cancer sur-gery.AIM To validate the applicability of the SIRI in assessing the survival of gastric cancer patients and evaluate the clinical contribution of preoperative SIRI levels to predicting long-term tumor outcomes in patients,who received robotic radical gastric cancer surgery.METHODS Initially,an exhaustive retrieval was performed in the PubMed,the Cochrane Library,EMBASE,Web of Science,and Scopus databases to identify relevant studies.Subsequently,a meta-analysis was executed on 6 cohort studies iden-tifying the value of the SIRI in assessing the survival of gastric cancer patients.Additionally,the clinical data of 161 patients undergoing robotic radical gastric cancer surgery were retrospectively analyzed to evaluate their clinicopathological characteristics and relevant laboratory indicators.The association between preoperative SIRI levels and 5-year overall survival(OS)and disease-free survival(DFS)was assessed.RESULTS The findings demonstrated an extensive connection between SIRI values and the outcome of patients with gastric cancer.Preoperative SIRI levels were identified as an independent hazard feature for both OS and DFS among those who received robotic surgery for gastric cancer.SIRI levels in gastric cancer patients were observed to be associated with the presence of comorbidities,T-stage,carcinoembryonic antigen levels,the development of early serious postoperative complications,and the rate of lymph node metastasis.CONCLUSION SIRI values are correlated with adverse in the gastric cancer population and have the potential to be utilized in predicting long-term oncological survival in patients who undergo robotic radical gastric cancer surgery.
基金Supported by the Nn10 Program of Harbin Medical University Cancer Hospital,China,No.Nn10 PY 2017-03.
文摘BACKGROUND Although immune checkpoint inhibitors(ICIs)have demonstrated significant survival benefits in some patients diagnosed with gastric cancer(GC),existing prognostic markers are not universally applicable to all patients with advanced GC.AIM To investigate biomarkers that predict prognosis in GC patients treated with ICIs and develop accurate predictive models.METHODS Data from 273 patients diagnosed with GC and distant metastasis,who un-derwent≥1 cycle(s)of ICIs therapy were included in this study.Patients were randomly divided into training and test sets at a ratio of 7:3.Training set data were used to develop the machine learning models,and the test set was used to validate their predictive ability.Shapley additive explanations were used to provide insights into the best model.RESULTS Among the 273 patients with GC treated with ICIs in this study,112 died within 1 year,and 129 progressed within the same timeframe.Five features related to overall survival and 4 related to progression-free survival were identified and used to construct eXtreme Gradient Boosting(XGBoost),logistic regression,and decision tree.After comprehensive evaluation,XGBoost demonstrated good accuracy in predicting overall survival and progression-free survival.CONCLUSION The XGBoost model aided in identifying patients with GC who were more likely to benefit from ICIs therapy.Patient nutritional status may,to some extent,reflect prognosis.
文摘BACKGROUND Gastric cancer is a kind of malignant tumor which is prevalent all over the world.Although some progress has been made in the treatment of gastric cancer,its prognosis is still not optimistic,so it is of great significance to find reliable prog-nostic indicators to guide the treatment and management of patients with gastric cancer.AIM To explore the relationship between serum levels of five biomarkers[carcinoem-bryonic antigen(CEA),carbohydrate antigen(CA)19-9,CA72-4,CA24-2,and ferritin]and prognosis in patients with gastric cancer.METHODS This study included 200 patients with gastric adenocarcinoma,and conducted an in-depth analysis of their baseline characteristics,relationship between tumor markers and staging,and prognosis.The study found that CA19-9 has a signi-ficant correlation with tumor stage,the average levels of CA24-2,CEA,CA72-4 and ferritin were slightly increased disregarding the stage of tumor.Survival analysis showed that increases in CEA,CA19-9,CA24-2,and ferritin were all associated with shortened overall survival of patients.Further multivariate ana-lysis revealed that elevated serum CA72-4 levels were an inde-pendent adverse prognostic factor.RESULTS This study reveals that there is a significant correlation between the expression levels of serum tumor markers CEA,CA19-9,CA72-4,CA24-2 and ferritin in patients with gastric cancer and prognosis,and can be used as important indicators for prognostic evaluation of gastric cancer.In particular,markers that appear abnormally elevated initially may help identify gastric cancer patients with poor prognosis.CONCLUSION Serum CEA and CA19-9 play an important role in the prognosis assessment of gastric cancer,and are effective tools to guide clinical practice and optimize individualized treatment strategies for gastric cancer patients.
基金supported by grant from the National Key R&D Program of China(grant number:2017YFC0908300)the Fun-damental Research Funds for the Central Universities(grant number:3332023136).
文摘Objective:Accurate prognosis prediction is critical for individualized-therapy making of gastric cancer patients.We aimed to develop and test 6-month,1-,2-,3-,5-,and 10-year overall survival(OS)and cancer-specific survival(CSS)prediction models for gastric cancer patients following gastrectomy.Methods:We derived and tested Survival Quilts,a machine learning-based model,to develop 6-month,1-,2-,3-,5-,and 10-year OS and CSS prediction models.Gastrectomy patients in the development set(n=20,583)and the internal validation set(n=5,106)were recruited from the Surveillance,Epidemiology,and End Re-sults(SEER)database,while those in the external validation set(n=6,352)were recruited from the China National Cancer Center Gastric Cancer(NCCGC)database.Furthermore,we selected gastrectomy patients with-out neoadjuvant therapy as a subgroup to train and test the prognostic models in order to keep the accuracy of tumor-node-metastasis(TNM)stage.Prognostic performances of these OS and CSS models were assessed using the Concordance Index(C-index)and area under the curve(AUC)values.Results:The machine learning model had a consistently high accuracy in predicting 6-month,1-,2-,3-,5-,and 10-year OS in the SEER development set(C-index=0.861,0.832,0.789,0.766,0.740,and 0.709;AUC=0.784,0.828,0.840,0.849,0.869,and 0.902,respectively),SEER validation set(C-index=0.782,0.739,0.712,0.698,0.681,and 0.660;AUC=0.751,0.772,0.767,0.762,0.766,and 0.787,respectively),and NCCGC set(C-index=0.691,0.756,0.751,0.737,0.722,and 0.701;AUC=0.769,0.788,0.790,0.790,0.787,and 0.788,respectively).The model was able to predict 6-month,1-,2-,3-,5-,and 10-year CSS in the SEER development set(C-index=0.879,0.858,0.820,0.802,0.784,and 0.774;AUC=0.756,0.827,0.852,0.863,0.874,and 0.884,respectively)and SEER validation set(C-index=0.790,0.763,0.741,0.729,0.718,and 0.708;AUC=0.706,0.758,0.767,0.766,0.766,and 0.764,respectively).In multivariate analysis,the high-risk group with risk score output by 5-year OS model was proved to be a strong survival predictor both in the SEER development set(hazard ratio[HR]=14.59,95%confidence interval[CI]:1.872-2.774,P<0.001),SEER validation set(HR=2.28,95%CI:13.089-16.293,P<0.001),and NCCGC set(HR=1.98,95%CI:1.617-2.437,P<0.001).We further explored the prognostic value of risk score resulted 5-year CSS model of gastrectomy patients,and found that high-risk group remained as an independent CSS factor in the SEER development set(HR=12.81,95%CI:11.568-14.194,P<0.001)and SEER validation set(HR=1.61,95%CI:1.338-1.935,P<0.001).Conclusion:Survival Quilts could allow accurate prediction of 6-month,1-,2-,3-,5-,and 10-year OS and CSS in gastric cancer patients following gastrectomy.
基金supported by Zhengzhou Major Collaborative Innovation Project(No.18XTZX12003)Key Projects of Discipline Construction in Zhengzhou University(No.XKZDJC202001)+1 种基金National Key Research and Development Program in China(No.2020YFC2006100)Medical Service Capacity Improvement Project of Henan Province in China(Grant Number Yu Wei Medicine[2017]No.66).
文摘Nicotinamide adenine dinucleotide(NAD+)plays an essential role in cellular metabolism,mitochondrial homeostasis,inflammation,and senescence.However,the role of NAD+-regulated genes,including coding and long non-coding genes in cancer development is poorly understood.We constructed a prediction model based on the expression level of NAD+metabolism-related genes(NMRGs).Furthermore,we validated the expression of NMRGs in gastric cancer(GC)tissues and cell lines;additionally,β-nicotinamide mononucleotide(NMN),a precursor of NAD+,was used to treat the GC cell lines to analyze its effects on the expression level of NMRGs lncRNAs and cellular proliferation,cell cycle,apoptosis,and senescence-associated secretory phenotype(SASP).A total of 13 NMRGs-related lncRNAs were selected to construct prognostic risk signatures,and patients with high-risk scores had a poor prognosis.Some immune checkpoint genes were upregulated in the high-risk group.In addition,cell cycle,epigenetics,and senescence were significantly downregulated in the high-risk group.Notably,we found that the levels of immune cell infiltration,including CD8 T cells,CD4 naïve T cells,CD4 memory-activated T cells,B memory cells,and naïve B cells,were significantly associated with risk scores.Furthermore,the treatment of NMN showed increased proliferation of AGS and MKN45 cells.In addition,the expression of SASP factors(IL6,IL8,IL10,TGF-β,and TNF-α)was significantly decreased after NMN treatment.We conclude that the lncRNAs associated with NAD+metabolism can potentially be used as biomarkers for predicting clinical outcomes of GC patients.
文摘BACKGROUND Early gastric cancer(EGC)is a common malignant tumor of the digestive system,and its lymph node metastasis and survival prognosis have been concerning.By retrospectively analyzing the clinical data of EGC patients,we can better under-stand the status of lymph node metastasis and its impact on survival and prog-nosis.AIM To evaluate the prognosis of EGC patients and the factors that affect lymph node METHODS The clinicopathological data of 1011 patients with EGC admitted to our hospital between January 2015 and December 2023 were collected in a retrospective cohort study.There were 561 males and 450 females.The mean age was 58±11 years.The patient underwent radical gastrectomy.The status of lymph node metastasis in each group was determined according to the pathological examination results of surgical specimens.The outcomes were as follows:(1)Lymph node metastasis in EGC patients;(2)Analysis of influencing factors of lymph node metastasis in EGC;and(3)Analysis of prognostic factors in patients with EGC.Normally distributed measurement data are expressed as mean±SD,and a t test was used for comparisons between groups.The data are expressed as absolute numbers or percentages,and the chi-square test was used for comparisons between groups.Rank data were compared using a nonparametric rank sum test.A log-rank test and a logistic regression model were used for univariate analysis.A logistic stepwise regression model and a Cox stepwise regression model were used for multivariate analysis.The Kaplan-Meier method was used to calculate the survival rate and construct survival curves.A log-rank test was used for survival analysis.RESULTS Analysis of influencing factors of lymph node metastasis in EGC.The results of the multifactor analysis showed that tumor length and diameter,tumor site,tumor invasion depth,vascular thrombus,and tumor differentiation degree were independent influencing factors for lymph node metastasis in patients with EGC(odds ratios=1.80,1.49,2.65,5.76,and 0.60;95%CI:1.29–2.50,1.11–2.00,1.81–3.88,3.87-8.59,and 0.48-0.76,respectively;P<0.05).Analysis of prognostic factors in patients with EGC.All 1011 patients with EGC were followed up for 43(0–13)months.The 3-year overall survival rate was 97.32%.Multivariate analysis revealed that age>60 years and lymph node metastasis were independent risk factors for prognosis in patients with EGC(hazard ratio=9.50,2.20;95%CI:3.31-27.29,1.00-4.87;P<0.05).Further analysis revealed that the 3-year overall survival rates of gastric cancer patients aged>60 years and≤60 years were 99.37%and 94.66%,respectively,and the difference was statistically significant(P<0.05).The 3-year overall survival rates of patients with and without lymph node metastasis were 95.42%and 97.92%,respectively,and the difference was statistically significant(P<0.05).CONCLUSION The lymph node metastasis rate of EGC patients was 23.64%.Tumor length,tumor site,tumor infiltration depth,vascular cancer thrombin,and tumor differentiation degree were found to be independent factors affecting lymph node metastasis in EGC patients.Age>60 years and lymph node metastasis are independent risk factors for EGC prognosis.
文摘BACKGROUND The hemoglobin,albumin,lymphocyte,and platelet(HALP)score,derived from a composite evaluation of markers reflecting the tumor-inflammation relationship and nutritional status,has been substantiated as a noteworthy prognostic determinant for diverse malignancies.AIM To investigate how the HALP score relates to prognosis in patients with metastatic gastric cancer.METHODS The cutoff values for the HALP score,neutrophil/lymphocyte ratio,and platelet/lymphocyte ratio were determined using receiver operating characteristic analysis.Low HALP scores were defined as those less than 24.79 and high HALP scores as those greater than 24.79.RESULTS The study cohort comprised 147 patients and 110 of them(74.8%)were male.The patients'median age was 63(22-89)years.The median overall survival was significantly superior in the patients with high HALP scores than in those with low HALP scores(10.4 mo vs 7.5 mo,respectively;P<0.001)CONCLUSION The HALP score was found to be a prognostic factor in patients with metastatic gastric cancer.
文摘BACKGROUND Gastric cancer(GC)is a common malignant tumor of the digestive system with a high degree of malignancy.It usually develops insidiously without any specific symptoms in the early stages.As one of the diseases caused by abnormal gene changes,GC has abnormal expression of various oncogenes and products during its development.Tumor markers such as carcinoembryonic antigen(CEA),carbohydrate antigen 199(CA199)and carbohydrate antigen 724(CA724)are not expressed or lowly expressed in normal people,but significantly increased after carcinogenesis.Monitoring the changes in the levels of tumor markers such as CEA,CA199 and CA724 is conducive to early diagnosis and evaluation of the occurrence of some solid tumors.AIM To investigate the expression of CEA,CA199 and CA724 in GC and their correlation with clinical features,hoping to provide more effective markers for the early preventive diagnosis of GC.METHODS Of 87 patients with GC admitted to our hospital from September 2020 to December 2021 were included in the GC group,and another 80 healthy people who came to our hospital for physical examination with normal results during the same period were selected as the control group.The serum CEA,CA199,and CA724 levels were compared between the two groups,and the serum CEA,CA199,and CA724 levels were compared in patients with GC at different TNM stages,and the differences in the positive rates of CEA,CA199,and CA724 alone and in combination in detecting TNM stages of GC and GC were compared.In addition,the relationship between the levels of tumor markers CEA,CA199 and CA724 and the clinicopathological characteristics of GC patients was also analyzed.The relationship between the serum levels of CEA,CA199 and CA724 and the survival period of GC patients was analyzed by Pearson.RESULTS The serum levels of CEA,CA199 and CA724 in GC group were significantly higher than those in control group(P<0.05).With the increase of TNM stage,the serum CEA,CA199 and CA724 expression levels in GC patients increased significantly,and the differences between groups were statistically significant(P<0.05).The positive rate of the CA724 single test was higher than that of CEA and CA199 single test(P<0.05).The positive rate of the three combined tests was 95.40%(83/87),which was higher than that of CEA,CA199 and CA724 single tests.The difference was statistically significant(P<0.05).The combined detection positive rates of CEA,CA199,and CA724 in stages I,II,III,and IV of GC were 89.66%,93.10%,98.85%,and 100.00%respectively,all of which were higher than the individual detection rates of CEA,CA199,and CA724.The differences were statistically significant(P<0.05).There was no significant difference in serum CEA,CA199 and CA724 levels between GC patients with different genders,smoking history and alcohol history(P>0.05).However,the serum CEA,CA199 and CA724 levels were significantly higher in GC patients aged≥45 years,TNM stage III-IV,with lymph node metastasis and tumor diameter≥5 cm than in GC patients aged<45 years,TNM stage I-II,without lymph node metastasis and tumor diameter<5 cm(P<0.05).CONCLUSION The expression levels of serum tumor markers CEA,CA199 and CA724 in patients with GC are high and rise with the increase of TNM stage.The levels of CEA,CA199 and CA724 are related to age,TNM stage,lymph node metastasis and tumor diameter.The combined detection of CEA,CA199 and CA724 is helpful to improve the diagnostic accuracy of GC with high clinical guidance value.
文摘BACKGROUND Gastric cancer(GC)is a common malignant tumor of the digestive system.Disulfidptosis is a new programmed cell death mechanism,although its specific mechanism in GC is incompletely understood.AIM In this study,we used bioinformatics analysis to explore a disulfidptosis-based predictive model related to GC prognosis and to identify potential therapeutic targets and sensitive drugs for GC.METHODS We extracted GC-related data from The Cancer Genome Atlas and Gene Expression Omnibus databases.R software(version 4.2.1)was used for correlation analysis.RESULTS Through the above analysis,we found that the disulfidptosis related gene may be related to the prognosis of GC.Six genes,namely,PLS3,GRP,APOD,SGCE,COL8A1,and VAMP7,were found to constitute a predictive model for GC prognosis.APOD is a potential therapeutic target for treating GC.Bosutinib and other drugs are sensitive for the treatment of GC.CONCLUSION The results of this study indicate that disulfidptosis is related to the prognosis and treatment of GC,while APOD represents a potential therapeutic target for GC.
基金supported by the Natural Science Foundation of Zhejiang Province(HDMY22H160008)the Medical Science and Technology Project of Zhejiang Province(2022KY114)the National Natural Science Foundation of China(82204828).
文摘Aim:Scavenger receptor class B,type I(SR-BI)is an integral plasma membrane protein that has been reported to be overexpressed in various malignancies,such as renal cancer,breast cancer,and prostate cancer,and is an independent prognostic factor.However,the clinical value and expression of SR-BI in GC are unknown.Our research aimed to explore the role of SR-BI in combination with immune markers as a diagnostic and prognostic marker for gastric cancer(GC).Methods:GC tissues,paracancerous tissues,and clinicopathological data of 149 patients were collected.The expression level of SR-BI,Tumor-infiltrating lymphocytes(TILs),and PD-L1 were evaluated by immunohistochemistry(IHC).The associations of the SR-BI staining intensity with clinicopathological features and immune markers were determined by the chi-square test.Univariate and multivariate COX regression analyses were used to evaluate independent prognostic factors.Kaplan–Meier analyses were performed to plot the survival curve.Results:Our results indicated that SR-BI was expressed at higher levels in tumor tissues than in adjacent paracancerous tissues(p<0.001),and patients with high levels of SR-BI expression had a worse prognosis.Univariate and multivariate analyses revealed that high SR-BI expression was an independent factor for poor prognosis.The chi-square test determined that the expression of SR-BI was negatively correlated with CD4+T cells and CD8+T cells(CD4+T cells,p=0.013;CD8+T cells,p=0.021),and positively correlated with PD-L1(p=0.022).Finally,survival analysis revealed that CD4+T cells were associated with the prognosis of GC patients(p=0.019),and the combined survival analysis of SR-BI and CD4+T cells was also statistically significant(p=0.030).Conclusion:SR-BI is highly expressed in GC tissue and associated with poor prognosis.Moreover,SR-BI can also regulate the GC tumor immune microenvironment.
基金Supported by National Natural Science Foundation of China,No.81971489Natural Science Foundation of Guangdong Province,No.2022A1515011122。
文摘BACKGROUND Gastric cancer(GC)is a malignant tumor with high morbidity and mortality.Expression of COL5A2 is significantly elevated in GC.Abnormal expression of noncoding RNAs(ncRNAs)have been found in GC,including microRNA(miRNA)and long noncoding RNA(lncRNA).Competing endogenous RNA network plays an important regulatory role in GC.However,its specific regulatory mechanism has not been elucidated.AIM To gain insight into the ncRNA regulatory mechanism and immune microenvironment related to COL5A2 in GC.METHODS RNA sequencing data and clinical information from The Cancer Genome Atlas data portal were used to analyze the expressions of COL5A2,miRNA and lncRNA related to the prognosis of GC.Cox regression analysis and Kyoto Encyclopedia of Genes and Genomes analysis were performed to assess the risk factors and relevant function of COL5A2.StarBase was used to predict the interaction of miRNA–lncRNA or miRNA–mRNA in GC.The relationship between COL5A2,miR-144-3p and ENTPD1-AS1 were verified by dual luciferase reporter assay.The association of COL5A2 with immune cell infiltration were analyzed using the Tumor Immune Estimation Resource database and single sample gene set enrichment analysis.The expression of COL5A2 and macrophages in paired GC tissues were detected by immunohistochemical staining.RESULTS We verified that the upregulation of COL5A2 expression was associated with the prognosis of GC and was an independent risk factor for GC.miR-144-3p was downregulated and correlated with the prognosis of GC.miR-144-3p regulated the expression of COL5A2 through direct interaction with COL5A2.ENTPD1-AS1 was elevated in GC and competitively bound to miR-144-3p,thus inhibiting the expression of miR-144-3p.ENTPD1-AS1 enhanced the expression of COL5A2 through sponging miR-144-3p.Compared to paired normal tissue,COL5A2 expression was upregulated at the protein level,especially in the middle and late stages of GC.The high expression of COL5A2 was positively linked to macrophage infiltration in GC.CONCLUSION COL5A2 regulated by ENTPD1-AS1–miR-144-3p was associated with poor prognosis and macrophage infiltration in GC.This could be a new biomarker and therapeutic target in GC.
文摘BACKGROUND The prognostic assessment of patients after surgical resection of gastric cancer(GC)patients is critical.However,the role of the circadian clock gene NPAS2 expression in GC remains unknown.AIM To explore the relationship between NPAS2 and the survival prognosis of GC patients and clarify its role in evaluating GC prognosis.METHODS The tumor tissues and clinical data of 101 patients with GC were collected retrospectively.Immunohistochemical staining(IHC)was used to detect the expression of NPAS2 protein in GC and adjacent tissues.Univariate and multivariate Cox regression analysis was used to determine the independent prognostic factors of GC,and a nomogram prediction model was established.The receiver operating characteristic(ROC)curve,the ROC area under the curve,the calibration curve,and C-index were used to evaluate the predictive effectiveness of the model.Kaplan Meier analysis was used to compare the risk stratification of subgroups according to the median score in the nomogram model of each patient.RESULTS Microarray IHC analysis showed that the positive rate of NPAS2 protein expression in GC tissues was 65.35%,which was significantly higher than 30.69%in adjacent tissues.The high expression of NPAS2 was correlated with tumor-node-metastasis(TNM)stage(P<0.05),pN stage(P<0.05),metastasis(P<0.05),venous invasion(P<0.05),lymphatic invasion(P<0.05),and lymph node positive(P<0.05)of GC.Kaplan Meier survival analysis showed that the 3-year overall survival(OS)of patients with high NPAS2 expression was significantly shortened(P<0.0001).Univariate and multivariate COX regression analysis showed that TNM stage(P=0.009),metastasis(P=0.009),and NPAS2 expression(P=0.020)were independent prognostic factors of OS in GC patients for 3 years.The nomogram prediction model based on independent prognostic factors has a C-Index of 0.740(95%CI:0.713-0.767).Furthermore,subgroup analysis showed that the 3-year OS time of the high-risk group was significantly lower than that of the low-risk group(P<0.0001).CONCLUSION NPAS2 is highly expressed in GC tissues and is closely related to worse OS in patients.Therefore,the evaluation of NPAS2 expression may be a potential marker for GC prognosis evaluation.Notably,the nomogram model based on NPAS2 can improve the accuracy of GC prognosis prediction and assist clinicians in postoperative patient management and decision-making.
