In this editorial we comment on the article“Hotspots and frontiers of the rela-tionship between gastric cancer and depression:A bibliometric study”.Gastric cancer(GC)is a common malignancy in the digestive system wi...In this editorial we comment on the article“Hotspots and frontiers of the rela-tionship between gastric cancer and depression:A bibliometric study”.Gastric cancer(GC)is a common malignancy in the digestive system with increased mortality and morbidity rates globally.Standard treatments,such as gastrectomy,negatively impact patients'quality of life and beyond the physical strain,GC patients face psychological challenges,including anxiety and depression.The prevalence of depression can be as high as 57%,among gastrointestinal cancer patients.Due to the advancements in treatment effectiveness and increased 5-year overall survival rates,attention has shifted to managing psychological effects.However,the significance of managing the depression doesn’t lie solely in the need for a better psychological status.Depression leads to chronic stress acti-vating the sympathetic nervous system and the hypothalamus-pituitary-adrenal axis,leading release of catecholamines inducing tumor proliferation,migration,and metastasis,contributing to GC progression.The dysregulation of neurotrans-mitters and the involvement of various signaling pathways underscore the complex interplay between depression and GC.Comprehensive strategies are required to address the psychological aspects of GC,including region-specific interventions and increased monitoring for depression.Understanding the intricate relationship between depression and GC progression is essential for developing effective therapeutic strategies and improving overall outcomes for patients facing this complex disease.In this Editorial we delve into double role of depression in the pathogenesis of GC and as a complication of it.展开更多
BACKGROUND Human-derived gastric cancer organoids(GCOs)are widely used in gastric cancer research;however,the culture success rate is generally low.AIM To explore the potential influencing factors,and the literature o...BACKGROUND Human-derived gastric cancer organoids(GCOs)are widely used in gastric cancer research;however,the culture success rate is generally low.AIM To explore the potential influencing factors,and the literature on successful culture rates of GCOs was reviewed using meta-analysis.METHODS PubMed,Web of Science,and EMBASE were searched for studies.Two trained researchers selected the studies and extracted data.STATA 17.0 software was used for meta-analysis of the incidence of each outcome event.The adjusted Methodological Index for Non-Randomized Studies scale was used to assess the quality of the included studies.Funnel plots and Egger’s test were used to detect publication bias.Subgroup analyses were conducted for sex,tissue source,histo-logical classification,and the pathological tumor-node-metastasis(pTNM)cancer staging system.RESULTS Eight studies with a pooled success rate of 66.6%were included.GCOs derived from women and men had success rates of 67%and 46.7%,respectively.GCOs from surgery or biopsy/endoscopic submucosal dissection showed success rates of 70.9%and 53.7%,respectively.GCOs of poorly-differentiated,moderately-differentiated and signet-ring cell cancer showed success rates of 64.6%,31%,and 32.7%,respectively.GCOs with pTNM stages I-II and III-IV showed success rates of 38.3%and 65.2%,respectively.Y-27632 and non-Y-27632 use showed success rates of 58.2%and 70%,respectively.GCOs generated with collagenase were more successful than those constructed with Liberase TH and TrypLE(72.1%vs 71%,respectively).EDTA digestion showed a 50%lower success rate than other methods(P=0.04).CONCLUSION GCO establishment rate is low and varies by sex,tissue source,histological type,and pTNM stage.Omitting Y-27632,and using Liberase TH,TrypLE,or collagenase yields greater success than EDTA.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
Gastric cancer(GC)is a prevalent malignant tumor within the digestive system,with over 40%of new cases and deaths related to GC globally occurring in China.Despite advancements in treatment modalities,such as surgery ...Gastric cancer(GC)is a prevalent malignant tumor within the digestive system,with over 40%of new cases and deaths related to GC globally occurring in China.Despite advancements in treatment modalities,such as surgery supplemented by adjuvant radiotherapy or chemotherapeutic agents,the prognosis for GC remains poor.New targeted therapies and immunotherapies are currently under invest-igation,but no significant breakthroughs have been achieved.Studies have indicated that GC is a heterogeneous disease,encompassing multiple subtypes with distinct biological characteristics and roles.Consequently,personalized treatment based on clinical features,pathologic typing,and molecular typing is crucial for the diagnosis and management of precancerous lesions of gastric cancer(PLGC).Current research has categorized GC into four subtypes:Epstein-Barr virus-positive,microsatellite instability,genome stability,and chromosome instability(CIN).Technologies such as multi-omics analysis and gene sequencing are being employed to identify more suitable novel testing methods in these areas.Among these,ultrasensitive chromosomal aneuploidy detection(UCAD)can detect CIN at a genome-wide level in subjects using low-depth whole genome sequencing technology,in conjunction with bioinformatics analysis,to achieve qualitative and quantitative detection of chromosomal stability.This editorial reviews recent research advancements in UCAD technology for the diagnosis and management of PLGC.展开更多
Objective:To explore the effect and mechanism of prostaglandins D2(PGD2)on the stemness of gastric cancer stem cells(GCSCs).Methods:7901-GCSCs were enriched by serum-free culture method;then the positivity rate of CD4...Objective:To explore the effect and mechanism of prostaglandins D2(PGD2)on the stemness of gastric cancer stem cells(GCSCs).Methods:7901-GCSCs were enriched by serum-free culture method;then the positivity rate of CD44,a stemness marker,was detected by flow cytometry in serum-free cultured 7901-GCSCs;the sphere-forming ability was detected by the sphere-forming assay after stimulation with different concentrations of PGD2(2.5,5,10)μg/mL,and the expression of stemness-related indicators(OCT4,CD44)and autophagyrelated proteins(LC3,Beclin-1)after PGD2 stimulation was detected by the western blot assay in different concentrations.The expression of stemness-related indexes(OCT4,CD44)and autophagy-related proteins(LC3,Beclin-1)were detected by Western blot assay after stimulation with different concentrations of PGD2.The expression of autophagy-related proteins after stimulation with different concentrations of CQ(2.5,5,10)μM was detected by Western blot experiment.The protein expression of autophagy-related proteins(LC3,Beclin-1)and stemness-related indexes(OCT4,CD44)was detected by Western blot experiment after PGD2 as well as PGD2+CQ treatment.Results:Flow cytometry results showed that the expression of CD44 positivity was increased in serum-free cultured 7901-GCSCs compared with gastric cancer cells SGC-7901(P<0.05),which fulfilled the needs of subsequent experiments.The results of stem cell spheroid formation assay showed that the spheroid formation ability of 7901-GCSCs in the PGD2 group was significantly weakened compared with that of the DMSO group(P<0.05).Western blot results showed that the protein expression of stemness-related indexes(OCT4,CD44)was down-regulated in the 7901-GCSCs in the PGD2 group compared with that of the DMSO group(P<0.05),and the expression of autophagy-related proteins(LC3,Beclin-1)expression increased(P<0.05).Compared with the DMSO group,the expression of autophagy-related proteins(LC3,Beclin-1)was decreased in the CQ group(P<0.05).Western blot results also showed that the expression of cellular autophagy-related proteins and stemness-related indexes in the PGD2+CQ group was not significantly changed compared with that of the DMSO group(ns:the difference was not significant),suggesting that the CQ could block the effect of PGD2 on the expression of stemness markers in 7901-GCSCs.7901-GCSCs stemness inhibition.Conclusion:PGD2 may affect the stemness of 7901-GCSCs by regulating autophagy.展开更多
In this editorial we comment on the article published in the recent issue of the World Journal of Gastrointestinal Endoscopy 2023;15(11):634-680.Gastric cancer(GC)remains the fifth most common malignancy and the fourt...In this editorial we comment on the article published in the recent issue of the World Journal of Gastrointestinal Endoscopy 2023;15(11):634-680.Gastric cancer(GC)remains the fifth most common malignancy and the fourth leading cause of cancer-related death worldwide.The overall prevalence of GC has declined,although that of proximal GC has increased over time.Thus,a significant proportion of GC cases and deaths can be avoided if preventive interventions are taken.Early GC(EGC)is defined as GC confined to the mucosa or submucosa.Endoscopic resection is considered the most appropriate treatment for precancerous gastrointestinal lesions improving patient quality of life,with reduced rates of complications,shorter hospitalization period,and lower costs when compared to surgical resection.Endoscopic mucosal resection(EMR)and endoscopic sub-mucosal dissection(ESD)are representative endoscopic treatments for EGC and precancerous gastric lesions.Standard EMR implies injection of a saline solution into the sub-mucosal space,followed by excision of the lesion using a snare.Complete resection rates vary depending on the size and severity of the lesion.When using conventional EMR methods for lesions less than 1 cm in size,the complete resection rate is approximately 60%,whereas for lesions larger than 2 cm,the complete resection rate is low(20%-30%).ESD can be used to remove tumors exceeding 2 cm in diameter and lesions associated with ulcers or submucosal fibrosis.Compared with EMR,ESD has higher en bloc resection rates(90.2%vs 51.7%),higher complete resection rates(82.1 vs 42.2%),and lower recurrence rates(0.65%vs 6.05%).Thus,innovative techniques have been introduced.展开更多
Objective:To evaluate the anticancer effect of ellagic acid on gastric cancer cells.Methods:MTT assay was used to evaluate the effect of ellagic acid at different concentrations(0.5-100μg/mL)on gastric cancer AGS cel...Objective:To evaluate the anticancer effect of ellagic acid on gastric cancer cells.Methods:MTT assay was used to evaluate the effect of ellagic acid at different concentrations(0.5-100μg/mL)on gastric cancer AGS cells.RT-qPCR and Western blot analyses were applied to assess apoptosis(BCL-2,CASP-3,and BAX)and autophagy(LC3,ATG5,and BECN1)in AGS cells treated with ellagic acid.The expression of invasion-related markers including TP53,CDKN2A,and PTEN was determined.In addition,cell cycle markers including cyclin A,B,D,and E were measured by ELISA.Oxidative stress markers were evaluated using spectrophotometry.Results:Ellagic acid inhibited the proliferation of AGS cells in a concentration-and time-dependent manner.The expression of BCL-2 was significantly decreased(P<0.05)and CASP-3 and BAX were markedly increased(P<0.01)in AGS cells treated with ellagic acid.However,this compound induced no significant changes in the expression levels of LC3,ATG5,and BECN1(P>0.05).Moreover,the oxidative stress markers including SOD,TAC,and MDA were increased by ellagic acid(P<0.01).Conclusions:Ellagic acid can inhibit cell proliferation,induce apoptosis,and modulate oxidative stress in AGS cells.However,further in vivo and molecular studies are needed to verify its anticancer efficacy.展开更多
In this editorial,we comment on the article entitled“Advances and key focus areas in gastric cancer immunotherapy:A comprehensive scientometric and clinical trial review(1999-2023),”which was published in the recent...In this editorial,we comment on the article entitled“Advances and key focus areas in gastric cancer immunotherapy:A comprehensive scientometric and clinical trial review(1999-2023),”which was published in the recent issue of the World Journal of Gastroenterology.We focused on the results of the authors’bibliometric analysis concerning gastric cancer immunotherapy,which they analyzed in depth by compiling the relevant publications of the last 20 years.Before that,we briefly describe the most recent data concerning the epidemiological parameters of gastric cancer(GC)in different countries,attempting to give an interpretation based on the etiological factors involved in the etiopathogenesis of the neoplasm.We then briefly discuss the conservative treatment(chemotherapy)of the various forms of this malignant neoplasm.We describe the treatment of resectable tumors,locally advanced neoplasms,and unresectable(advanced)cases.Special attention is given to modern therapeutic approaches with emphasis on immunotherapy,which seems to be the future of GC treatment,especially in combination with chemotherapy.There is also a thorough analysis of the results of the study under review in terms of the number of scientific publications,the countries in which the studies were conducted,the authors,and the scientific centers of origin,as well as the clinical studies in progress.Finally,an attempt is made to draw some conclusions and to point out possible future directions.展开更多
This letter is intended to arouse your interest in a recent review of comprehensive scientometrics and clinical trials on immunotherapy for gastric cancer(GC).Our study reviews recent advances in immunotherapy in the ...This letter is intended to arouse your interest in a recent review of comprehensive scientometrics and clinical trials on immunotherapy for gastric cancer(GC).Our study reviews recent advances in immunotherapy in the field of GC and highlights its new prospects as a treatment for GC.Our research reveals China’s leadership in this field,as well as new therapeutic strategies such as immune checkpoint inhibitors,cellular immunotherapy,and vaccines.The combined findings highlight the potential of immunotherapy to improve survival and quality of life in patients with stomach cancer.We believe that this study will provide important guidance for the future direction of the GC treatment field.展开更多
BACKGROUND Gastric cancer(GC)is associated with high mortality rates.Bile acids(BAs)reflux is a well-known risk factor for GC,but the specific mechanism remains unclear.During GC development in both humans and animals...BACKGROUND Gastric cancer(GC)is associated with high mortality rates.Bile acids(BAs)reflux is a well-known risk factor for GC,but the specific mechanism remains unclear.During GC development in both humans and animals,BAs serve as signaling molecules that induce metabolic reprogramming.This confers additional cancer phenotypes,including ferroptosis sensitivity.Ferroptosis is a novel mode of cell death characterized by lipid peroxidation that contributes universally to malignant progression.However,it is not fully defined if BAs can influence GC progression by modulating ferroptosis.AIM To reveal the mechanism of BAs regulation in ferroptosis of GC cells.METHODS In this study,we treated GC cells with various stimuli and evaluated the effect of BAs on the sensitivity to ferroptosis.We used gain and loss of function assays to examine the impacts of farnesoid X receptor(FXR)and BTB and CNC homology 1(BACH1)overexpression and knockdown to obtain further insights into the molecular mechanism involved.RESULTS Our data suggested that BAs could reverse erastin-induced ferroptosis in GC cells.This effect correlated with increased glutathione(GSH)concentrations,a reduced GSH to oxidized GSH ratio,and higher GSH peroxidase 4(GPX4)expression levels.Subsequently,we confirmed that BAs exerted these effects by activating FXR,which markedly increased the expression of GSH synthetase and GPX4.Notably,BACH1 was detected as an essential intermediate molecule in the promotion of GSH synthesis by BAs and FXR.Finally,our results suggested that FXR could significantly promote GC cell proliferation,which may be closely related to its anti-ferroptosis effect.CONCLUSION This study revealed for the first time that BAs could inhibit ferroptosis sensitivity through the FXR-BACH1-GSHGPX4 axis in GC cells.This work provided new insights into the mechanism associated with BA-mediated promotion of GC and may help identify potential therapeutic targets for GC patients with BAs reflux.展开更多
After the study of circulating tumor cells in blood through liquid biopsy(LB),this technique has evolved to encompass the analysis of multiple materials originating from the tumor,such as nucleic acids,extracellular v...After the study of circulating tumor cells in blood through liquid biopsy(LB),this technique has evolved to encompass the analysis of multiple materials originating from the tumor,such as nucleic acids,extracellular vesicles,tumor-educated platelets,and other metabolites.Additionally,research has extended to include the examination of samples other than blood or plasma,such as saliva,gastric juice,urine,or stool.LB techniques are diverse,intricate,and variable.They must be highly sensitive,and pre-analytical,patient,and tumor-related factors significantly influence the detection threshold,diagnostic method selection,and potential results.Consequently,the implementation of LB in clinical practice still faces several challenges.The potential applications of LB range from early cancer detection to guiding targeted therapy or immunotherapy in both early and advanced cancer cases,monitoring treatment response,early identification of relapses,or assessing patient risk.On the other hand,gastric cancer(GC)is a disease often diagnosed at advanced stages.Despite recent advances in molecular understanding,the currently available treatment options have not substantially improved the prognosis for many of these patients.The application of LB in GC could be highly valuable as a non-invasive method for early diagnosis and for enhancing the management and outcomes of these patients.In this comprehensive review,from a pathologist’s perspective,we provide an overview of the main options available in LB,delve into the fundamental principles of the most studied techniques,explore the potential utility of LB application in the context of GC,and address the obstacles that need to be overcome in the future to make this innovative technique a game-changer in cancer diagnosis and treatment within clinical practice.展开更多
The high mortality rate associated with gastric cancer(GC)has resulted in an urgent need to identify novel therapeutic targets for GC.This study aimed to investigate whether GAIP interacting protein,C terminus 1(GIPC1...The high mortality rate associated with gastric cancer(GC)has resulted in an urgent need to identify novel therapeutic targets for GC.This study aimed to investigate whether GAIP interacting protein,C terminus 1(GIPC1)represents a therapeutic target and its regulating mechanism in GC.GIPC1 expression was elevated in GC tissues,liver metastasis tissues,and lymph node metastases.GIPC1 knockdown or GIPC1 blocking peptide blocked the platelet-derived growth factor receptor(PDGFR)/PI3K/AKT signaling pathway,and inhibited the proliferation and migration of GC cells.Conversely,GIPC1 overexpression markedly activated the PDGFR/PI3K/AKT signaling pathway,and promoted GC cell proliferation and migration.Furthermore,platelet-derived growth factor subunit BB(PDGF-BB)cytokines and the AKT inhibitor attenuated the effect of differential GIPC1 expression.Moreover,GIPC1 silencing decreased tumor growth and migration in BALB/c nude mice,while GIPC1 overexpression had contrasting effects.Taken together,our findings suggest that GIPC1 functions as an oncogene in GC and plays a central role in regulating cell proliferation and migration via the PDGFR/PI3K/AKT signaling pathway.展开更多
BACKGROUND The development and progression of gastric cancer(GC)are closely linked to the nutritional status of patients.Although immunotherapy has been demonstrated to be clinically effective,the relationships of sar...BACKGROUND The development and progression of gastric cancer(GC)are closely linked to the nutritional status of patients.Although immunotherapy has been demonstrated to be clinically effective,the relationships of sarcopenia and myosteatosis with the use of immune checkpoint inhibitors(ICIs)in patients with gastric cancer remain to be characterized.METHODS We performed a retrospective study of patients who were undergoing immuno-therapy for GC.For the evaluation of sarcopenia,the optimal cut-off value for the skeletal muscle index was established using receiver operating characteristic analysis of data obtained from pre-treatment computed tomography images at the L3 vertebral level.Myosteatosis was defined using the mean skeletal muscle density(SMD),with a threshold value of<41 Hounsfield units(HU)for patients with a body mass index(BMI)<25 kg/m^(2)and<33 HU for those with a BMI≥25 kg/m^(2).The log-rank test was used to compare progression-free survival(PFS)and overall survival(OS),and a Cox proportional hazard model was used to identify prognostic factors.Nomograms were developed to predict the PFS and OS of patients on the basis of the results of multivariate analyses.RESULTS We studied 115 patients who were undergoing ICI therapy for GC,of whom 27.4%had sarcopenia and 29.8%had myosteatosis.Patients with sarcopenia or myosteatosis had significantly shorter PFS and OS than those without these conditions.Furthermore,both sarcopenia and myosteatosis were found to be independent predictors of PFS and OS in patients with GC administering an ICI.The prediction models created for PFS and OS were associated with C-indexes of 0.758 and 0.781,respectively.CONCLUSION The presence of sarcopenia or myosteatosis is a reliable predictor of the clinical outcomes of patients with GC who are undergoing treatment with an ICI.展开更多
BACKGROUND Lymphovascular invasion(LVI)and perineural invasion(PNI)are important prognostic factors for gastric cancer(GC)that indicate an increased risk of metastasis and poor outcomes.Accurate preoperative predictio...BACKGROUND Lymphovascular invasion(LVI)and perineural invasion(PNI)are important prognostic factors for gastric cancer(GC)that indicate an increased risk of metastasis and poor outcomes.Accurate preoperative prediction of LVI/PNI status could help clinicians identify high-risk patients and guide treatment deci-sions.However,prior models using conventional computed tomography(CT)images to predict LVI or PNI separately have had limited accuracy.Spectral CT provides quantitative enhancement parameters that may better capture tumor invasion.We hypothesized that a predictive model combining clinical and spectral CT parameters would accurately preoperatively predict LVI/PNI status in GC patients.AIM To develop and test a machine learning model that fuses spectral CT parameters and clinical indicators to predict LVI/PNI status accurately.METHODS This study used a retrospective dataset involving 257 GC patients(training cohort,n=172;validation cohort,n=85).First,several clinical indicators,including serum tumor markers,CT-TN stages and CT-detected extramural vein invasion(CT-EMVI),were extracted,as were quantitative spectral CT parameters from the delineated tumor regions.Next,a two-step feature selection approach using correlation-based methods and information gain ranking inside a 10-fold cross-validation loop was utilized to select informative clinical and spectral CT parameters.A logistic regression(LR)-based nomogram model was subsequently constructed to predict LVI/PNI status,and its performance was evaluated using the area under the receiver operating characteristic curve(AUC).RESULTS In both the training and validation cohorts,CT T3-4 stage,CT-N positive status,and CT-EMVI positive status are more prevalent in the LVI/PNI-positive group and these differences are statistically significant(P<0.05).LR analysis of the training group showed preoperative CT-T stage,CT-EMVI,single-energy CT values of 70 keV of venous phase(VP-70 keV),and the ratio of standardized iodine concentration of equilibrium phase(EP-NIC)were independent influencing factors.The AUCs of VP-70 keV and EP-NIC were 0.888 and 0.824,respectively,which were slightly greater than those of CT-T and CT-EMVI(AUC=0.793,0.762).The nomogram combining CT-T stage,CT-EMVI,VP-70 keV and EP-NIC yielded AUCs of 0.918(0.866-0.954)and 0.874(0.784-0.936)in the training and validation cohorts,which are significantly higher than using each of single independent factors(P<0.05).CONCLUSION The study found that using portal venous and EP spectral CT parameters allows effective preoperative detection of LVI/PNI in GC,with accuracy boosted by integrating clinical markers.展开更多
BACKGROUND Laparoscopic radical gastrectomy is widely used,and perioperative complications have become a highly concerned issue.AIM To develop a predictive model for complications in laparoscopic radical gastrectomy f...BACKGROUND Laparoscopic radical gastrectomy is widely used,and perioperative complications have become a highly concerned issue.AIM To develop a predictive model for complications in laparoscopic radical gastrectomy for gastric cancer to better predict the likelihood of complications in gastric cancer patients within 30 days after surgery,guide perioperative treatment strategies for gastric cancer patients,and prevent serious complications.METHODS In total,998 patients who underwent laparoscopic radical gastrectomy for gastric cancer at 16 Chinese medical centers were included in the training group for the complication model,and 398 patients were included in the validation group.The clinicopathological data and 30-d postoperative complications of gastric cancer patients were collected.Three machine learning methods,lasso regression,random forest,and artificial neural networks,were used to construct postoperative complication prediction models for laparoscopic distal gastrectomy and laparoscopic total gastrectomy,and their prediction efficacy and accuracy were evaluated.RESULTS The constructed complication model,particularly the random forest model,could better predict serious complications in gastric cancer patients undergoing laparoscopic radical gastrectomy.It exhibited stable performance in external validation and is worthy of further promotion in more centers.CONCLUSION Using the risk factors identified in multicenter datasets,highly sensitive risk prediction models for complications following laparoscopic radical gastrectomy were established.We hope to facilitate the diagnosis and treatment of preoperative and postoperative decision-making by using these models.展开更多
As important messengers of intercellular communication,exosomes can regulate local and distant cellular communication by transporting specific exosomal con-tents and can also promote or suppress the development and pr...As important messengers of intercellular communication,exosomes can regulate local and distant cellular communication by transporting specific exosomal con-tents and can also promote or suppress the development and progression of gas-tric cancer(GC)by regulating the growth and proliferation of tumor cells,the tumor-related immune response and tumor angiogenesis.Exosomes transport bioactive molecules including DNA,proteins,and RNA(coding and noncoding)from donor cells to recipient cells,causing reprogramming of the target cells.In this review,we will describe how exosomes regulate the cellular immune respon-se,tumor angiogenesis,proliferation and metastasis of GC cells,and the role and mechanism of exosome-based therapy in human cancer.We will also discuss the potential application value of exosomes as biomarkers in the diagnosis and treat-ment of GC and their relationship with drug resistance.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(GC)is one of the most aggressive malignancies with limited therapeutic options and a poor prognosis.Resveratrol,a non-flavonoid poly-phenolic compound found in a variety of Chinese medicinal ...BACKGROUND Gastric cancer(GC)is one of the most aggressive malignancies with limited therapeutic options and a poor prognosis.Resveratrol,a non-flavonoid poly-phenolic compound found in a variety of Chinese medicinal materials,has shown excellent anti-GC effect.However,its exact mechanisms of action in GC have not been clarified.AIM To identify the effects of resveratrol on GC progression and explore the related molecular mechanisms.METHODS Action targets of resveratrol and GC-related targets were screened from public databases.The overlapping targets between the two were confirmed using a Venn diagram,and a“Resveratrol-Target-GC”network was constructed using Cyto-scape software version 3.9.1.The protein-protein interaction(PPI)network was constructed using STRING database and core targets were identified by PPI network analysis.The Database for Annotation,Visualization and Integrated A total of 378 resveratrol action targets and 2154 GC disease targets were obtained from public databases,and 181 intersection targets between the two were screened by Venn diagram.The top 20 core targets were identified by PPI network analysis of the overlapping targets.GO function analysis mainly involved protein binding,identical protein binding,cytoplasm,nucleus,negative regulation of apoptotic process and response to xenobiotic stimulus.KEGG enrichment analysis suggested that the involved signaling pathways mainly included PI3K-AKT signaling pathway,MAPK signaling pathway,IL-17 signaling pathway,TNF signaling pathway,ErbB signaling pathway,etc.FBJ murine osteosarcoma viral oncogene homolog(FOS)and matrix metallopeptidase 9(MMP9)were selected by differential expression analysis,and they were closely associated with immune infiltration.Molecular docking results showed that resveratrol docked well with these two targets.Resveratrol treatment arrested the cell cycle at the S phase,induced apoptosis,and weakened viability,migration and invasion in a dose-dependent manner.Furthermore,resveratrol could exhibit anti-GC effect by regulating FOS and MMP9 expression.CONCLUSION The anti-GC effects of resveratrol are related to the inhibition of cell proliferation,migration,invasion and induction of cell cycle arrest and apoptosis by targeting FOS and MMP9.展开更多
BACKGROUND Gastric cancer(GC)is a prevalent malignant tumor of the gastrointestinal system.ZNF710 is a transcription factor(TF),and zinc finger protein 710(ZNF710)-AS1-201 is an immune-related long noncoding RNA(lncRN...BACKGROUND Gastric cancer(GC)is a prevalent malignant tumor of the gastrointestinal system.ZNF710 is a transcription factor(TF),and zinc finger protein 710(ZNF710)-AS1-201 is an immune-related long noncoding RNA(lncRNA)that is upregulated in GC cells.AIM To assess the correlation between ZNF710-AS1-201 and immune microenvir-onment features and to investigate the roles of ZNF710-AS1-201 in the invasion and metastasis processes of GC cells.METHODS We obtained data from The Cancer Genome Atlas and Wujin Hospital.We assessed cell growth,migration,invasion,and programmed cell death using cell counting kit-8,EdU,scratch,Transwell,and flow cytometry assays.Quantitative real-time polymerase chain reaction(qRT-PCR)was used to identify the potential downstream targets of ZNF710-AS1-201.RESULTS In GC tissues with low ZNF710-AS1-201 expression,immunoassays detected significant infiltration of various antitumor immune cells,such as memory CD8 T cells and activated CD4 T cells.In the low-expression group,the half-maximal inhibitory concentrations(IC_(50)s)of 5-fluorouracil,cisplatin,gemcitabine,and trametinib were lower,whereas the IC_(50)s of dasatinib and vorinostat were higher.The malignant degree of GC was higher and the stage was later in the high-expression group.Additionally,patients with high expression of ZNF710-AS1-201 had lower overall survival and disease-free survival rates.In vitro,the overexpression of ZNF710-AS1-201 greatly enhanced growth,metastasis,and infiltration while suppressing cell death in HGC-27 cells.In contrast,the reduced expression of ZNF710-AS1-201 greatly hindered cell growth,enhanced apoptosis,and suppressed the metastasis and invasion of MKN-45 cells.The expression changes in ZNF710 were significant,but the corresponding changes in isocitrate dehydrogenase-2,Semaphorin 4B,ARHGAP10,RGMB,hsa-miR-93-5p,and ZNF710-AS1-202 were not consistent or statistically significant after overexpression or knockdown of ZNF710-AS1-201,as determined by qRT-PCR.CONCLUSION Immune-related lncRNA ZNF710-AS1-201 facilitates the metastasis and invasion of GC cells.It appears that ZNF710-AS1-201 and ZNF710 have potential as effective targets for therapeutic intervention in GC.Nevertheless,it is still necessary to determine the specific targets of the ZNF710 TF.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
文摘In this editorial we comment on the article“Hotspots and frontiers of the rela-tionship between gastric cancer and depression:A bibliometric study”.Gastric cancer(GC)is a common malignancy in the digestive system with increased mortality and morbidity rates globally.Standard treatments,such as gastrectomy,negatively impact patients'quality of life and beyond the physical strain,GC patients face psychological challenges,including anxiety and depression.The prevalence of depression can be as high as 57%,among gastrointestinal cancer patients.Due to the advancements in treatment effectiveness and increased 5-year overall survival rates,attention has shifted to managing psychological effects.However,the significance of managing the depression doesn’t lie solely in the need for a better psychological status.Depression leads to chronic stress acti-vating the sympathetic nervous system and the hypothalamus-pituitary-adrenal axis,leading release of catecholamines inducing tumor proliferation,migration,and metastasis,contributing to GC progression.The dysregulation of neurotrans-mitters and the involvement of various signaling pathways underscore the complex interplay between depression and GC.Comprehensive strategies are required to address the psychological aspects of GC,including region-specific interventions and increased monitoring for depression.Understanding the intricate relationship between depression and GC progression is essential for developing effective therapeutic strategies and improving overall outcomes for patients facing this complex disease.In this Editorial we delve into double role of depression in the pathogenesis of GC and as a complication of it.
基金Supported by National Natural Science Foundation of China,No.82174309 and No.81973774National Administration of Traditional Chinese Medicine:2019 Project of Building Evidence-Based Practice Capacity for TCM,No.2019XZZX-XH013Shuguang Hospital Siming Foundation Research Special Project,No.SGKJ-202304.
文摘BACKGROUND Human-derived gastric cancer organoids(GCOs)are widely used in gastric cancer research;however,the culture success rate is generally low.AIM To explore the potential influencing factors,and the literature on successful culture rates of GCOs was reviewed using meta-analysis.METHODS PubMed,Web of Science,and EMBASE were searched for studies.Two trained researchers selected the studies and extracted data.STATA 17.0 software was used for meta-analysis of the incidence of each outcome event.The adjusted Methodological Index for Non-Randomized Studies scale was used to assess the quality of the included studies.Funnel plots and Egger’s test were used to detect publication bias.Subgroup analyses were conducted for sex,tissue source,histo-logical classification,and the pathological tumor-node-metastasis(pTNM)cancer staging system.RESULTS Eight studies with a pooled success rate of 66.6%were included.GCOs derived from women and men had success rates of 67%and 46.7%,respectively.GCOs from surgery or biopsy/endoscopic submucosal dissection showed success rates of 70.9%and 53.7%,respectively.GCOs of poorly-differentiated,moderately-differentiated and signet-ring cell cancer showed success rates of 64.6%,31%,and 32.7%,respectively.GCOs with pTNM stages I-II and III-IV showed success rates of 38.3%and 65.2%,respectively.Y-27632 and non-Y-27632 use showed success rates of 58.2%and 70%,respectively.GCOs generated with collagenase were more successful than those constructed with Liberase TH and TrypLE(72.1%vs 71%,respectively).EDTA digestion showed a 50%lower success rate than other methods(P=0.04).CONCLUSION GCO establishment rate is low and varies by sex,tissue source,histological type,and pTNM stage.Omitting Y-27632,and using Liberase TH,TrypLE,or collagenase yields greater success than EDTA.
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.
文摘Gastric cancer(GC)is a prevalent malignant tumor within the digestive system,with over 40%of new cases and deaths related to GC globally occurring in China.Despite advancements in treatment modalities,such as surgery supplemented by adjuvant radiotherapy or chemotherapeutic agents,the prognosis for GC remains poor.New targeted therapies and immunotherapies are currently under invest-igation,but no significant breakthroughs have been achieved.Studies have indicated that GC is a heterogeneous disease,encompassing multiple subtypes with distinct biological characteristics and roles.Consequently,personalized treatment based on clinical features,pathologic typing,and molecular typing is crucial for the diagnosis and management of precancerous lesions of gastric cancer(PLGC).Current research has categorized GC into four subtypes:Epstein-Barr virus-positive,microsatellite instability,genome stability,and chromosome instability(CIN).Technologies such as multi-omics analysis and gene sequencing are being employed to identify more suitable novel testing methods in these areas.Among these,ultrasensitive chromosomal aneuploidy detection(UCAD)can detect CIN at a genome-wide level in subjects using low-depth whole genome sequencing technology,in conjunction with bioinformatics analysis,to achieve qualitative and quantitative detection of chromosomal stability.This editorial reviews recent research advancements in UCAD technology for the diagnosis and management of PLGC.
基金Natural Science Foundation of Anhui Province(No.1908085MH258)Scientific Research and Innovation Project of Bengbu Medical College(No.Byycxz21004)。
文摘Objective:To explore the effect and mechanism of prostaglandins D2(PGD2)on the stemness of gastric cancer stem cells(GCSCs).Methods:7901-GCSCs were enriched by serum-free culture method;then the positivity rate of CD44,a stemness marker,was detected by flow cytometry in serum-free cultured 7901-GCSCs;the sphere-forming ability was detected by the sphere-forming assay after stimulation with different concentrations of PGD2(2.5,5,10)μg/mL,and the expression of stemness-related indicators(OCT4,CD44)and autophagyrelated proteins(LC3,Beclin-1)after PGD2 stimulation was detected by the western blot assay in different concentrations.The expression of stemness-related indexes(OCT4,CD44)and autophagy-related proteins(LC3,Beclin-1)were detected by Western blot assay after stimulation with different concentrations of PGD2.The expression of autophagy-related proteins after stimulation with different concentrations of CQ(2.5,5,10)μM was detected by Western blot experiment.The protein expression of autophagy-related proteins(LC3,Beclin-1)and stemness-related indexes(OCT4,CD44)was detected by Western blot experiment after PGD2 as well as PGD2+CQ treatment.Results:Flow cytometry results showed that the expression of CD44 positivity was increased in serum-free cultured 7901-GCSCs compared with gastric cancer cells SGC-7901(P<0.05),which fulfilled the needs of subsequent experiments.The results of stem cell spheroid formation assay showed that the spheroid formation ability of 7901-GCSCs in the PGD2 group was significantly weakened compared with that of the DMSO group(P<0.05).Western blot results showed that the protein expression of stemness-related indexes(OCT4,CD44)was down-regulated in the 7901-GCSCs in the PGD2 group compared with that of the DMSO group(P<0.05),and the expression of autophagy-related proteins(LC3,Beclin-1)expression increased(P<0.05).Compared with the DMSO group,the expression of autophagy-related proteins(LC3,Beclin-1)was decreased in the CQ group(P<0.05).Western blot results also showed that the expression of cellular autophagy-related proteins and stemness-related indexes in the PGD2+CQ group was not significantly changed compared with that of the DMSO group(ns:the difference was not significant),suggesting that the CQ could block the effect of PGD2 on the expression of stemness markers in 7901-GCSCs.7901-GCSCs stemness inhibition.Conclusion:PGD2 may affect the stemness of 7901-GCSCs by regulating autophagy.
文摘In this editorial we comment on the article published in the recent issue of the World Journal of Gastrointestinal Endoscopy 2023;15(11):634-680.Gastric cancer(GC)remains the fifth most common malignancy and the fourth leading cause of cancer-related death worldwide.The overall prevalence of GC has declined,although that of proximal GC has increased over time.Thus,a significant proportion of GC cases and deaths can be avoided if preventive interventions are taken.Early GC(EGC)is defined as GC confined to the mucosa or submucosa.Endoscopic resection is considered the most appropriate treatment for precancerous gastrointestinal lesions improving patient quality of life,with reduced rates of complications,shorter hospitalization period,and lower costs when compared to surgical resection.Endoscopic mucosal resection(EMR)and endoscopic sub-mucosal dissection(ESD)are representative endoscopic treatments for EGC and precancerous gastric lesions.Standard EMR implies injection of a saline solution into the sub-mucosal space,followed by excision of the lesion using a snare.Complete resection rates vary depending on the size and severity of the lesion.When using conventional EMR methods for lesions less than 1 cm in size,the complete resection rate is approximately 60%,whereas for lesions larger than 2 cm,the complete resection rate is low(20%-30%).ESD can be used to remove tumors exceeding 2 cm in diameter and lesions associated with ulcers or submucosal fibrosis.Compared with EMR,ESD has higher en bloc resection rates(90.2%vs 51.7%),higher complete resection rates(82.1 vs 42.2%),and lower recurrence rates(0.65%vs 6.05%).Thus,innovative techniques have been introduced.
基金supported by the Heilongjiang Provincial Natural Science Foundation of China(LH2022H063).
文摘Objective:To evaluate the anticancer effect of ellagic acid on gastric cancer cells.Methods:MTT assay was used to evaluate the effect of ellagic acid at different concentrations(0.5-100μg/mL)on gastric cancer AGS cells.RT-qPCR and Western blot analyses were applied to assess apoptosis(BCL-2,CASP-3,and BAX)and autophagy(LC3,ATG5,and BECN1)in AGS cells treated with ellagic acid.The expression of invasion-related markers including TP53,CDKN2A,and PTEN was determined.In addition,cell cycle markers including cyclin A,B,D,and E were measured by ELISA.Oxidative stress markers were evaluated using spectrophotometry.Results:Ellagic acid inhibited the proliferation of AGS cells in a concentration-and time-dependent manner.The expression of BCL-2 was significantly decreased(P<0.05)and CASP-3 and BAX were markedly increased(P<0.01)in AGS cells treated with ellagic acid.However,this compound induced no significant changes in the expression levels of LC3,ATG5,and BECN1(P>0.05).Moreover,the oxidative stress markers including SOD,TAC,and MDA were increased by ellagic acid(P<0.01).Conclusions:Ellagic acid can inhibit cell proliferation,induce apoptosis,and modulate oxidative stress in AGS cells.However,further in vivo and molecular studies are needed to verify its anticancer efficacy.
文摘In this editorial,we comment on the article entitled“Advances and key focus areas in gastric cancer immunotherapy:A comprehensive scientometric and clinical trial review(1999-2023),”which was published in the recent issue of the World Journal of Gastroenterology.We focused on the results of the authors’bibliometric analysis concerning gastric cancer immunotherapy,which they analyzed in depth by compiling the relevant publications of the last 20 years.Before that,we briefly describe the most recent data concerning the epidemiological parameters of gastric cancer(GC)in different countries,attempting to give an interpretation based on the etiological factors involved in the etiopathogenesis of the neoplasm.We then briefly discuss the conservative treatment(chemotherapy)of the various forms of this malignant neoplasm.We describe the treatment of resectable tumors,locally advanced neoplasms,and unresectable(advanced)cases.Special attention is given to modern therapeutic approaches with emphasis on immunotherapy,which seems to be the future of GC treatment,especially in combination with chemotherapy.There is also a thorough analysis of the results of the study under review in terms of the number of scientific publications,the countries in which the studies were conducted,the authors,and the scientific centers of origin,as well as the clinical studies in progress.Finally,an attempt is made to draw some conclusions and to point out possible future directions.
基金the Discipline Promotion Program of Shanghai Fourth People’s Hospital,No.SY-XKZT-2020-1021.
文摘This letter is intended to arouse your interest in a recent review of comprehensive scientometrics and clinical trials on immunotherapy for gastric cancer(GC).Our study reviews recent advances in immunotherapy in the field of GC and highlights its new prospects as a treatment for GC.Our research reveals China’s leadership in this field,as well as new therapeutic strategies such as immune checkpoint inhibitors,cellular immunotherapy,and vaccines.The combined findings highlight the potential of immunotherapy to improve survival and quality of life in patients with stomach cancer.We believe that this study will provide important guidance for the future direction of the GC treatment field.
基金Supported by the Major Basic Research Project of Natural Science Foundation of Shandong Province,No.ZR2020ZD15.
文摘BACKGROUND Gastric cancer(GC)is associated with high mortality rates.Bile acids(BAs)reflux is a well-known risk factor for GC,but the specific mechanism remains unclear.During GC development in both humans and animals,BAs serve as signaling molecules that induce metabolic reprogramming.This confers additional cancer phenotypes,including ferroptosis sensitivity.Ferroptosis is a novel mode of cell death characterized by lipid peroxidation that contributes universally to malignant progression.However,it is not fully defined if BAs can influence GC progression by modulating ferroptosis.AIM To reveal the mechanism of BAs regulation in ferroptosis of GC cells.METHODS In this study,we treated GC cells with various stimuli and evaluated the effect of BAs on the sensitivity to ferroptosis.We used gain and loss of function assays to examine the impacts of farnesoid X receptor(FXR)and BTB and CNC homology 1(BACH1)overexpression and knockdown to obtain further insights into the molecular mechanism involved.RESULTS Our data suggested that BAs could reverse erastin-induced ferroptosis in GC cells.This effect correlated with increased glutathione(GSH)concentrations,a reduced GSH to oxidized GSH ratio,and higher GSH peroxidase 4(GPX4)expression levels.Subsequently,we confirmed that BAs exerted these effects by activating FXR,which markedly increased the expression of GSH synthetase and GPX4.Notably,BACH1 was detected as an essential intermediate molecule in the promotion of GSH synthesis by BAs and FXR.Finally,our results suggested that FXR could significantly promote GC cell proliferation,which may be closely related to its anti-ferroptosis effect.CONCLUSION This study revealed for the first time that BAs could inhibit ferroptosis sensitivity through the FXR-BACH1-GSHGPX4 axis in GC cells.This work provided new insights into the mechanism associated with BA-mediated promotion of GC and may help identify potential therapeutic targets for GC patients with BAs reflux.
文摘After the study of circulating tumor cells in blood through liquid biopsy(LB),this technique has evolved to encompass the analysis of multiple materials originating from the tumor,such as nucleic acids,extracellular vesicles,tumor-educated platelets,and other metabolites.Additionally,research has extended to include the examination of samples other than blood or plasma,such as saliva,gastric juice,urine,or stool.LB techniques are diverse,intricate,and variable.They must be highly sensitive,and pre-analytical,patient,and tumor-related factors significantly influence the detection threshold,diagnostic method selection,and potential results.Consequently,the implementation of LB in clinical practice still faces several challenges.The potential applications of LB range from early cancer detection to guiding targeted therapy or immunotherapy in both early and advanced cancer cases,monitoring treatment response,early identification of relapses,or assessing patient risk.On the other hand,gastric cancer(GC)is a disease often diagnosed at advanced stages.Despite recent advances in molecular understanding,the currently available treatment options have not substantially improved the prognosis for many of these patients.The application of LB in GC could be highly valuable as a non-invasive method for early diagnosis and for enhancing the management and outcomes of these patients.In this comprehensive review,from a pathologist’s perspective,we provide an overview of the main options available in LB,delve into the fundamental principles of the most studied techniques,explore the potential utility of LB application in the context of GC,and address the obstacles that need to be overcome in the future to make this innovative technique a game-changer in cancer diagnosis and treatment within clinical practice.
基金supported by the Natural Science Foundation of Xiamen City(3502Z20227307)the National Natural Science Foundation of China(81472458,82372809)the Special Fund for Public Welfare Research Institutes of Fujian Province(2023R1001001,2023R1001003,2023R1035).
文摘The high mortality rate associated with gastric cancer(GC)has resulted in an urgent need to identify novel therapeutic targets for GC.This study aimed to investigate whether GAIP interacting protein,C terminus 1(GIPC1)represents a therapeutic target and its regulating mechanism in GC.GIPC1 expression was elevated in GC tissues,liver metastasis tissues,and lymph node metastases.GIPC1 knockdown or GIPC1 blocking peptide blocked the platelet-derived growth factor receptor(PDGFR)/PI3K/AKT signaling pathway,and inhibited the proliferation and migration of GC cells.Conversely,GIPC1 overexpression markedly activated the PDGFR/PI3K/AKT signaling pathway,and promoted GC cell proliferation and migration.Furthermore,platelet-derived growth factor subunit BB(PDGF-BB)cytokines and the AKT inhibitor attenuated the effect of differential GIPC1 expression.Moreover,GIPC1 silencing decreased tumor growth and migration in BALB/c nude mice,while GIPC1 overexpression had contrasting effects.Taken together,our findings suggest that GIPC1 functions as an oncogene in GC and plays a central role in regulating cell proliferation and migration via the PDGFR/PI3K/AKT signaling pathway.
基金This study was approved by the Ethics Committee of Harbin Medical University Cancer Hospital.
文摘BACKGROUND The development and progression of gastric cancer(GC)are closely linked to the nutritional status of patients.Although immunotherapy has been demonstrated to be clinically effective,the relationships of sarcopenia and myosteatosis with the use of immune checkpoint inhibitors(ICIs)in patients with gastric cancer remain to be characterized.METHODS We performed a retrospective study of patients who were undergoing immuno-therapy for GC.For the evaluation of sarcopenia,the optimal cut-off value for the skeletal muscle index was established using receiver operating characteristic analysis of data obtained from pre-treatment computed tomography images at the L3 vertebral level.Myosteatosis was defined using the mean skeletal muscle density(SMD),with a threshold value of<41 Hounsfield units(HU)for patients with a body mass index(BMI)<25 kg/m^(2)and<33 HU for those with a BMI≥25 kg/m^(2).The log-rank test was used to compare progression-free survival(PFS)and overall survival(OS),and a Cox proportional hazard model was used to identify prognostic factors.Nomograms were developed to predict the PFS and OS of patients on the basis of the results of multivariate analyses.RESULTS We studied 115 patients who were undergoing ICI therapy for GC,of whom 27.4%had sarcopenia and 29.8%had myosteatosis.Patients with sarcopenia or myosteatosis had significantly shorter PFS and OS than those without these conditions.Furthermore,both sarcopenia and myosteatosis were found to be independent predictors of PFS and OS in patients with GC administering an ICI.The prediction models created for PFS and OS were associated with C-indexes of 0.758 and 0.781,respectively.CONCLUSION The presence of sarcopenia or myosteatosis is a reliable predictor of the clinical outcomes of patients with GC who are undergoing treatment with an ICI.
基金Supported by Science and Technology Project of Fujian Province,No.2022Y0025.
文摘BACKGROUND Lymphovascular invasion(LVI)and perineural invasion(PNI)are important prognostic factors for gastric cancer(GC)that indicate an increased risk of metastasis and poor outcomes.Accurate preoperative prediction of LVI/PNI status could help clinicians identify high-risk patients and guide treatment deci-sions.However,prior models using conventional computed tomography(CT)images to predict LVI or PNI separately have had limited accuracy.Spectral CT provides quantitative enhancement parameters that may better capture tumor invasion.We hypothesized that a predictive model combining clinical and spectral CT parameters would accurately preoperatively predict LVI/PNI status in GC patients.AIM To develop and test a machine learning model that fuses spectral CT parameters and clinical indicators to predict LVI/PNI status accurately.METHODS This study used a retrospective dataset involving 257 GC patients(training cohort,n=172;validation cohort,n=85).First,several clinical indicators,including serum tumor markers,CT-TN stages and CT-detected extramural vein invasion(CT-EMVI),were extracted,as were quantitative spectral CT parameters from the delineated tumor regions.Next,a two-step feature selection approach using correlation-based methods and information gain ranking inside a 10-fold cross-validation loop was utilized to select informative clinical and spectral CT parameters.A logistic regression(LR)-based nomogram model was subsequently constructed to predict LVI/PNI status,and its performance was evaluated using the area under the receiver operating characteristic curve(AUC).RESULTS In both the training and validation cohorts,CT T3-4 stage,CT-N positive status,and CT-EMVI positive status are more prevalent in the LVI/PNI-positive group and these differences are statistically significant(P<0.05).LR analysis of the training group showed preoperative CT-T stage,CT-EMVI,single-energy CT values of 70 keV of venous phase(VP-70 keV),and the ratio of standardized iodine concentration of equilibrium phase(EP-NIC)were independent influencing factors.The AUCs of VP-70 keV and EP-NIC were 0.888 and 0.824,respectively,which were slightly greater than those of CT-T and CT-EMVI(AUC=0.793,0.762).The nomogram combining CT-T stage,CT-EMVI,VP-70 keV and EP-NIC yielded AUCs of 0.918(0.866-0.954)and 0.874(0.784-0.936)in the training and validation cohorts,which are significantly higher than using each of single independent factors(P<0.05).CONCLUSION The study found that using portal venous and EP spectral CT parameters allows effective preoperative detection of LVI/PNI in GC,with accuracy boosted by integrating clinical markers.
基金Natural Science Foundation of Fujian Province,No.2021J011360,and No.2020J011230Natural Science Foundation of Xiamen,China,No.3502Z20214ZD1018,and No.3502Z20227096+2 种基金Medical Innovation Project of Fujian Provincial Health Commission,No.2021CXB019Youth Scientific Research Project of Fujian Provincial Health Commission,No.2022QNB013Bethune Charitable Foundation,No.HZB-20190528-10.
文摘BACKGROUND Laparoscopic radical gastrectomy is widely used,and perioperative complications have become a highly concerned issue.AIM To develop a predictive model for complications in laparoscopic radical gastrectomy for gastric cancer to better predict the likelihood of complications in gastric cancer patients within 30 days after surgery,guide perioperative treatment strategies for gastric cancer patients,and prevent serious complications.METHODS In total,998 patients who underwent laparoscopic radical gastrectomy for gastric cancer at 16 Chinese medical centers were included in the training group for the complication model,and 398 patients were included in the validation group.The clinicopathological data and 30-d postoperative complications of gastric cancer patients were collected.Three machine learning methods,lasso regression,random forest,and artificial neural networks,were used to construct postoperative complication prediction models for laparoscopic distal gastrectomy and laparoscopic total gastrectomy,and their prediction efficacy and accuracy were evaluated.RESULTS The constructed complication model,particularly the random forest model,could better predict serious complications in gastric cancer patients undergoing laparoscopic radical gastrectomy.It exhibited stable performance in external validation and is worthy of further promotion in more centers.CONCLUSION Using the risk factors identified in multicenter datasets,highly sensitive risk prediction models for complications following laparoscopic radical gastrectomy were established.We hope to facilitate the diagnosis and treatment of preoperative and postoperative decision-making by using these models.
文摘As important messengers of intercellular communication,exosomes can regulate local and distant cellular communication by transporting specific exosomal con-tents and can also promote or suppress the development and progression of gas-tric cancer(GC)by regulating the growth and proliferation of tumor cells,the tumor-related immune response and tumor angiogenesis.Exosomes transport bioactive molecules including DNA,proteins,and RNA(coding and noncoding)from donor cells to recipient cells,causing reprogramming of the target cells.In this review,we will describe how exosomes regulate the cellular immune respon-se,tumor angiogenesis,proliferation and metastasis of GC cells,and the role and mechanism of exosome-based therapy in human cancer.We will also discuss the potential application value of exosomes as biomarkers in the diagnosis and treat-ment of GC and their relationship with drug resistance.
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Natural Science Foundation of Hebei Province,No.H2018307071Traditional Chinese Medicine Research Plan Project in Hebei Province,No.2022122Hebei Provincial Science and Technology Program,No.17397763D.
文摘BACKGROUND Gastric cancer(GC)is one of the most aggressive malignancies with limited therapeutic options and a poor prognosis.Resveratrol,a non-flavonoid poly-phenolic compound found in a variety of Chinese medicinal materials,has shown excellent anti-GC effect.However,its exact mechanisms of action in GC have not been clarified.AIM To identify the effects of resveratrol on GC progression and explore the related molecular mechanisms.METHODS Action targets of resveratrol and GC-related targets were screened from public databases.The overlapping targets between the two were confirmed using a Venn diagram,and a“Resveratrol-Target-GC”network was constructed using Cyto-scape software version 3.9.1.The protein-protein interaction(PPI)network was constructed using STRING database and core targets were identified by PPI network analysis.The Database for Annotation,Visualization and Integrated A total of 378 resveratrol action targets and 2154 GC disease targets were obtained from public databases,and 181 intersection targets between the two were screened by Venn diagram.The top 20 core targets were identified by PPI network analysis of the overlapping targets.GO function analysis mainly involved protein binding,identical protein binding,cytoplasm,nucleus,negative regulation of apoptotic process and response to xenobiotic stimulus.KEGG enrichment analysis suggested that the involved signaling pathways mainly included PI3K-AKT signaling pathway,MAPK signaling pathway,IL-17 signaling pathway,TNF signaling pathway,ErbB signaling pathway,etc.FBJ murine osteosarcoma viral oncogene homolog(FOS)and matrix metallopeptidase 9(MMP9)were selected by differential expression analysis,and they were closely associated with immune infiltration.Molecular docking results showed that resveratrol docked well with these two targets.Resveratrol treatment arrested the cell cycle at the S phase,induced apoptosis,and weakened viability,migration and invasion in a dose-dependent manner.Furthermore,resveratrol could exhibit anti-GC effect by regulating FOS and MMP9 expression.CONCLUSION The anti-GC effects of resveratrol are related to the inhibition of cell proliferation,migration,invasion and induction of cell cycle arrest and apoptosis by targeting FOS and MMP9.
基金Changzhou Sci and Tech Program,No.CJ20220008Young Talent Development Plan of Changzhou Health Commission,No.CZQM2020118+2 种基金Changzhou High-Level Medical Talents Training Project,No.2022CZBJ105Cultivation Project of Changzhou Medical Center,Nanjing Medical University,No.CMCB202211Development Foundation of Affiliated Hospital of Xuzhou Medical University,No.XYFC202304,and No.XYFM202307。
文摘BACKGROUND Gastric cancer(GC)is a prevalent malignant tumor of the gastrointestinal system.ZNF710 is a transcription factor(TF),and zinc finger protein 710(ZNF710)-AS1-201 is an immune-related long noncoding RNA(lncRNA)that is upregulated in GC cells.AIM To assess the correlation between ZNF710-AS1-201 and immune microenvir-onment features and to investigate the roles of ZNF710-AS1-201 in the invasion and metastasis processes of GC cells.METHODS We obtained data from The Cancer Genome Atlas and Wujin Hospital.We assessed cell growth,migration,invasion,and programmed cell death using cell counting kit-8,EdU,scratch,Transwell,and flow cytometry assays.Quantitative real-time polymerase chain reaction(qRT-PCR)was used to identify the potential downstream targets of ZNF710-AS1-201.RESULTS In GC tissues with low ZNF710-AS1-201 expression,immunoassays detected significant infiltration of various antitumor immune cells,such as memory CD8 T cells and activated CD4 T cells.In the low-expression group,the half-maximal inhibitory concentrations(IC_(50)s)of 5-fluorouracil,cisplatin,gemcitabine,and trametinib were lower,whereas the IC_(50)s of dasatinib and vorinostat were higher.The malignant degree of GC was higher and the stage was later in the high-expression group.Additionally,patients with high expression of ZNF710-AS1-201 had lower overall survival and disease-free survival rates.In vitro,the overexpression of ZNF710-AS1-201 greatly enhanced growth,metastasis,and infiltration while suppressing cell death in HGC-27 cells.In contrast,the reduced expression of ZNF710-AS1-201 greatly hindered cell growth,enhanced apoptosis,and suppressed the metastasis and invasion of MKN-45 cells.The expression changes in ZNF710 were significant,but the corresponding changes in isocitrate dehydrogenase-2,Semaphorin 4B,ARHGAP10,RGMB,hsa-miR-93-5p,and ZNF710-AS1-202 were not consistent or statistically significant after overexpression or knockdown of ZNF710-AS1-201,as determined by qRT-PCR.CONCLUSION Immune-related lncRNA ZNF710-AS1-201 facilitates the metastasis and invasion of GC cells.It appears that ZNF710-AS1-201 and ZNF710 have potential as effective targets for therapeutic intervention in GC.Nevertheless,it is still necessary to determine the specific targets of the ZNF710 TF.
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.
