Esophageal squamous cell carcinoma(ESCC)is the major subtype of esophageal cancer that is prevalent in Eastern Asia.Despite recent advances in therapy,the outcome of ESCC patients is still dismal.MicroRNAs(miRNAs)are ...Esophageal squamous cell carcinoma(ESCC)is the major subtype of esophageal cancer that is prevalent in Eastern Asia.Despite recent advances in therapy,the outcome of ESCC patients is still dismal.MicroRNAs(miRNAs)are non-coding RNAs which can negatively modulate gene expression at the post-transcriptional level.The involvement and roles of miRNAs have become one of the hot topics of cancer research in recent years.In ESCC,genetic variations within miRNA coding genes were found to have distinct epidemiological significance in different populations.Dysregulated expression of several miRNAs was reported to be associated with therapeutic response.Functionally,miRNAs can act either in an oncogenic or a tumor-suppressive manner during tumorigenesis of ESCC by interrupting signaling pathways associated with cell proliferation,metabolism,cancer stemness,and resistance to chemo-or radiotherapy.Moreover,miRNAs modulate metastasis of ESCC by targeting genes that regulate cytoskeleton dynamics,extracellular matrix remodeling,epithelial-mesenchymal transition,and tumor microenvironment.Most importantly,mounting evidence suggests that inhibiting oncogenic miRNAs or restoring the loss of tumor-suppressive miRNAs has therapeutic potential in the treatment of ESCC.Here,we review and discuss recent studies on the significance,biological functions,and therapeutic potential of miRNAs in tumorigenesis and metastasis of ESCC.展开更多
Dysregulation of polycomb group protein Bmi-1 expression has been linked with an invasive phenotype of certain human cancers and poor prognosis of patients; however, the underlying mechanisms are
Wnt signaling are critical pathway involved in organ development, tumorigenesis, and cancer progression. WNT7A, a member of the Wnt family, remains poorly understood in terms of its role and the underlying molecular m...Wnt signaling are critical pathway involved in organ development, tumorigenesis, and cancer progression. WNT7A, a member of the Wnt family, remains poorly understood in terms of its role and the underlying molecular mechanisms it entails in head and neck squamous cell carcinoma (HNSCC). According to the Cancer Genome Atlas (TCGA), transcriptome sequencing data of HNSCC, the expression level of WNT7A in tumors was found to be higher than in adjacent normal tissues, which was validated using Real-time RT-PCR and immunohistochemistry. Unexpectedly, overexpression of WNT7A did not activate the canonical Wnt-β-catenin pathway in HNSCC. Instead, our findings suggested that WNT7A potentially activated the FZD7/JAK1/STAT3 signaling pathway, leading to enhanced cell proliferation, self-renewal, and resistance to apoptosis. Furthermore, in a patient-derived xenograft (PDX) tumor model, high expression of WNT7A and phosphorylated STAT3 was observed, which positively correlated with tumor progression.These findings underscore the significance of WNT7A in HNSCC progression and propose the targeting of key molecules within the FZD7/JAK1/STAT3 pathway as a promising strategy for precise treatment of HNSCC.展开更多
The interplay between DNA replication stress and immune microenvironment alterations is known to play a crucial role in colorectal tumorigenesis,but a comprehensive understanding of their association with and relevant...The interplay between DNA replication stress and immune microenvironment alterations is known to play a crucial role in colorectal tumorigenesis,but a comprehensive understanding of their association with and relevant biomarkers involved in colorectal tumorigenesis is lacking.To address this gap,we conducted a study aiming to investigate this association and identify relevant biomarkers.We analyzed transcriptomic and proteomic profiles of 904 colorectal tumor tissues and 342 normal tissues to examine pathway enrichment,biological activity,and the immune microenvironment.Additionally,we evaluated genetic effects of single variants and genes on colorectal cancer susceptibility using data from genome-wide association studies(GWASs)involving both East Asian(7062 cases and 195745 controls)and European(24476 cases and 23073 controls)populations.We employed mediation analysis to infer the causal pathway,and applied multiplex immunofluorescence to visualize colocalized biomarkers in colorectal tumors and immune cells.Our findings revealed that both DNA replication activity and the flap structure-specific endonuclease 1(FEN1)gene were significantly enriched in colorectal tumor tissues,compared with normal tissues.Moreover,a genetic variant rs4246215 G>T in FEN1 was associated with a decreased risk of colorectal cancer(odds ratio=0.94,95%confidence interval:0.90–0.97,P_(meta)=4.70×10^(-9)).Importantly,we identified basophils and eosinophils that both exhibited a significantly decreased infiltration in colorectal tumors,and were regulated by rs4246215 through causal pathways involving both FEN1 and DNA replication.In conclusion,this trans-omics incorporating GWAS data provides insights into a plausible pathway connecting DNA replication and immunity,expanding biological knowledge of colorectal tumorigenesis and therapeutic targets.展开更多
Greenblatt and his team have unveiled vertebral skeletal stem cells(vSSCs)as a critical player in the landscape of bone metastasis.This commentary delves into the transformative discoveries surrounding vSSCs,emphasizi...Greenblatt and his team have unveiled vertebral skeletal stem cells(vSSCs)as a critical player in the landscape of bone metastasis.This commentary delves into the transformative discoveries surrounding vSSCs,emphasizing their distinct role in bone metastasis compared to other stem cell lineages.We illuminate the unique properties and functions of vSSCs,which may account for the elevated susceptibility of vertebral bones to metastatic invasion.Furthermore,we explore the exciting therapeutic horizons opened by this newfound understanding.These include potential interventions targeting vSSCs,modulation of associated signaling pathways,and broader implications for the treatment and management of bone metastasis.By shedding light on these game-changing insights,we hope to pave the way for novel strategies that could revolutionize the prognosis and treatment landscape for cancer patients with metastatic bone disease.展开更多
Objective:To explore the regulatory mechanism of NUDT5 in glioblastoma multiforme(GBM).Methods:GEPIA database was used to predict the expressions of NUDT5 and tripartite motif family proteins 47(TRIM47)in GBM patients...Objective:To explore the regulatory mechanism of NUDT5 in glioblastoma multiforme(GBM).Methods:GEPIA database was used to predict the expressions of NUDT5 and tripartite motif family proteins 47(TRIM47)in GBM patients.RT-qPCR and Western blot analyses were performed to examine NUDT5 expression in GBM cells.LN-229 cell proliferation,migration as well as invasion were estimated by CCK-8,colony formation,wound healing,and Transwell assays following interference with NUDT5.ECAR assay,L-lactic acid kit,glucose detection kit,and ATP detection kit were applied for the detection of glycolysis-related indexes.Co-immunoprecipitation experiment was carried out to verify the relationship between NUDT5 and TRIM47.Results:GEPIA database showed that NUDT5 expression was significantly increased in GBM patients.Inhibiting the expression of NUDT5 in GBM cells significantly suppressed the viability,proliferation,invasion,migration,and glycolysis of GBM cells.Moreover,TRIM47 was highly expressed in GBM cells and interacted with NUDT5.Overexpression of TRIM47 partially reversed the inhibitory effect of NUDT5 downregulation on the proliferation,metastasis,and glycolysis of GBM cells.Conclusions:NUDT5 promotes the growth,metastasis,and Warburg effect of GBM cells by upregulating TRIM47.Both NUDT5 and TRIM47 can be used as targets for GMB treatment.展开更多
BACKGROUND Duodenal cancer is one of the most common subtypes of small intestinal cancer,and distant metastasis(DM)in this type of cancer still leads to poor prognosis.Although nomograms have recently been used in tum...BACKGROUND Duodenal cancer is one of the most common subtypes of small intestinal cancer,and distant metastasis(DM)in this type of cancer still leads to poor prognosis.Although nomograms have recently been used in tumor areas,no studies have focused on the diagnostic and prognostic evaluation of DM in patients with primary duodenal cancer.AIM To develop and evaluate nomograms for predicting the risk of DM and person-alized prognosis in patients with duodenal cancer.METHODS Data on duodenal cancer patients diagnosed between 2010 and 2019 were extracted from the Surveillance,Epidemiology,and End Results database.Univariate and multivariate logistic regression analyses were used to identify independent risk factors for DM in patients with duodenal cancer,and univariate and multivariate Cox proportional hazards regression analyses were used to determine independent prognostic factors in duodenal cancer patients with DM.Two novel nomograms were established,and the results were evaluated by receiver operating characteristic(ROC)curves,calibration curves,and decision curve analysis(DCA).RESULTS A total of 2603 patients with duodenal cancer were included,of whom 457 cases(17.56%)had DM at the time of diagnosis.Logistic analysis revealed independent risk factors for DM in duodenal cancer patients,including gender,grade,tumor size,T stage,and N stage(P<0.05).Univariate and multivariate COX analyses further identified independent prognostic factors for duodenal cancer patients with DM,including age,histological type,T stage,tumor grade,tumor size,bone metastasis,chemotherapy,and surgery(P<0.05).The accuracy of the nomograms was validated in the training set,validation set,and expanded testing set using ROC curves,calibration curves,and DCA curves.The results of Kaplan-Meier survival curves(P<0.001)indicated that both nomograms accurately predicted the occurrence and prognosis of DM in patients with duodenal cancer.CONCLUSION The two nomograms are expected as effective tools for predicting DM risk in duodenal cancer patients and offering personalized prognosis predictions for those with DM,potentially enhancing clinical decision-making.展开更多
BACKGROUND Metastatic cardiac tumors are known to occur more frequently than primary cardiac tumors,however,they often remain asymptomatic and are commonly dis-covered on autopsy.Malignant tumors with a relatively hig...BACKGROUND Metastatic cardiac tumors are known to occur more frequently than primary cardiac tumors,however,they often remain asymptomatic and are commonly dis-covered on autopsy.Malignant tumors with a relatively high frequency of cardiac metastasis include mesothelioma,melanoma,lung cancer,and breast cancer,whereas reports of esophageal cancer with cardiac metastasis are rare.CASE SUMMARY The case of a 60-year-old man who complained of dysphagia is presented.Upper gastrointestinal endoscopy showed a submucosal tumor-like elevated lesion in the esophagus causing stenosis.Contrast-enhanced computed tomography showed left atrial compression due to the esophageal tumor,multiple liver and lung metastases,and a left pleural effusion.Pathological examination of a biopsy speci-men from the esophageal tumor showed spindle-shaped cells,raising suspicion of esophageal sarcoma.The disease progressed rapidly,and systemic chemotherapy was deemed necessary,however,due to his poor general condition,adminis-tration of cytotoxic agents was considered difficult.Given his high Combined Positive Score,nivolumab was administered,however,the patient soon died from the disease.The autopsy confirmed spindle cell carcinoma(SCC)of the esophagus and cardiac metastasis with similar histological features.Cancer stem cell markers,ZEB1 and TWIST,were positive in both the primary tumor and the cardiac metastasis.CONCLUSION To the best of our knowledge,there have been no prior reports of cardiac metastasis of esophageal SCC.This case highlights our experience with a patient with esophageal SCC who progressed rapidly and died from the disease,with the autopsy examination showing cardiac metastasis.展开更多
BACKGROUND Esophageal squamous cell carcinoma(ESCC)is one of the most common malignancies worldwide,and its development comprises a multistep process from intraepithelial neoplasia(IN)to carcinoma(CA).However,the crit...BACKGROUND Esophageal squamous cell carcinoma(ESCC)is one of the most common malignancies worldwide,and its development comprises a multistep process from intraepithelial neoplasia(IN)to carcinoma(CA).However,the critical regulators and underlying molecular mechanisms remain largely unknown.AIM To explore the genes and infiltrating immune cells in the microenvironment that are associated with the multistage progression of ESCC to facilitate diagnosis and early intervention.METHODS A mouse model mimicking the multistage development of ESCC was established by providing warter containing 4-nitroquinoline 1-oxide(4NQO)to C57BL/6 mice.Moreover,we established a control group without 4NQO treatment of mice.Then,transcriptome sequencing was performed for esophageal tissues from patients with different pathological statuses,including low-grade IN(LGIN),high-grade IN(HGIN),and CA,and controlled normal tissue(NOR)samples.Differentially expressed genes(DEGs)were identified in the LGIN,HGIN,and CA groups,and the biological functions of the DEGs were analyzed via Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses.The CIBERSORT algorithm was used to detect the pattern of immune cell infilt-ration.Immunohistochemistry(IHC)was also conducted to validate our results.Finally,the Luminex multiplex cytokine analysis was utilized to measure the serum cytokine levels in the mice.RESULTS Compared with those in the NOR group,a total of 681541,and 840 DEGs were obtained in the LGIN,HGIN,and CA groups,respectively.Using the intersection of the three sets of DEGs,we identified 86 genes as key genes involved in the development of ESCC.Enrichment analysis revealed that these genes were enriched mainly in the keratinization,epidermal cell differentiation,and interleukin(IL)-17 signaling pathways.CIBERSORT analysis revealed that,compared with those in the NOR group,M0 and M1 macrophages in the 4NQO group showed stronger infiltration,which was validated by IHC.Serum cytokine analysis revealed that,compared with those in the NOR group,IL-1βand IL-6 were upregulated,while IL-10 was downregulated in the LGIN,HGIN,and CA groups.Moreover,the expression of the representative key genes,such as S100a8 and Krt6b,was verified in external human samples,and the results of immunohistochemical staining were consistent with the findings in mice.CONCLUSION We identified a set of key genes represented by S100a8 and Krt6b and investigated their potential biological functions.In addition,we found that macrophage infiltration and abnormal alterations in the levels of inflam-mation-associated cytokines,such as IL-1β,IL-6,and IL-10,in the peripheral blood may be closely associated with the development of ESCC.展开更多
Colorectal cancer liver metastasis(CRLM)presents a clinical challenge,and optimizing treatment strategies is crucial for improving patient outcomes.Surgical resection,a key element in achieving prolonged survival,is o...Colorectal cancer liver metastasis(CRLM)presents a clinical challenge,and optimizing treatment strategies is crucial for improving patient outcomes.Surgical resection,a key element in achieving prolonged survival,is often linked to a heightened risk of recurrence.Acknowledging the potential benefits of preoperative neoadjuvant chemotherapy in managing resectable liver metastases,this approach has gained attention for its role in tumor downsizing,assessing biological behavior,and reducing the risk of postoperative recurrence.However,the use of neoadjuvant chemotherapy in initially resectable CRLM sparks ongoing debates.The balance between tumor reduction and the risk of hepatic injury,coupled with concerns about delaying surgery,necessitates a nuanced approach.This article explores recent research insights and draws upon the practical experiences at our center to address critical issues regarding considerations for initially resectable cases.Examining the criteria for patient selection and the judicious choice of neoadjuvant regimens are pivotal areas of discussion.Striking the right balance between maximizing treatment efficacy and minimizing adverse effects is imperative.The dynamic landscape of precision medicine is also reflected in the evolving role of gene testing,such as RAS/BRAF and PIK3CA,in tailoring neoadjuvant regimens.Furthermore,the review emphasizes the need for a multidisciplinary approach to navigate the comp-lexities of CRLM.Integrating technical expertise and biological insights is crucial in refining neoadjuvant strategies.The management of progression following neoadjuvant chemotherapy requires a tailored approach,acknowledging the diverse biological behaviors that may emerge.In conclusion,this review aims to provide a comprehensive perspective on the considerations,challenges,and advancements in the use of neoadjuvant chemotherapy for initially resectable CRLM.By combining evidencebased insights with practical experiences,we aspire to contribute to the ongoing discourse on refining treatment paradigms for improved outcomes in patients with CRLM.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
Objective:The aim was to analyse the clinical features of leptomeningeal metastasis with banded high signal in the brainstem.Methods:In this paper,we report two cases of lung adenocarcinoma with soft meningeal metasta...Objective:The aim was to analyse the clinical features of leptomeningeal metastasis with banded high signal in the brainstem.Methods:In this paper,we report two cases of lung adenocarcinoma with soft meningeal metastasis,collected from the First Affiliated Hospital of Hainan Medical College,and searched the databases of CNKI,Wanfang,VIP,PubMed,Web of Science,and other databases which reported the MRI manifestation of"brainstem bandlike high signal",and collected the patients'past medical history,symptoms,signs,genetic findings,cerebrospinal fluid manifestation,treatment,and prognosis.Result:A total of 28 patients were included,of whom 26 had a history of lung adenocarcinoma and 2 were found to have occupational changes in the lungs.Magnetic resonance imaging(MRI)showed a band-like high signal in the ventral part of the brainstem on T2-FLAIR,symmetrical on both sides,which could extend to the cerebellar peduncles,with high signals on diffusion-weighted imaging(DWI),low signals on apparent diffusion coefficient(ADC),and long T1 signals on T1-weighted imaging,long T2 signals on T2 weighted imaging,and no long T2 signals on enhancement scan.T1-weighted imaging was a long T1 signal,T2-weighted imaging was a long T2 signal,and no enhancement was seen on enhanced scanning.Conclusion:It is important to recognize leptomeningeal metastasis of lung cancer,and the non-enhancing band of high signal in the brainstem on T2-FLAIR and DWI is likely to be the characteristic manifestation of leptomeningeal metastasis of non-small cell lung cancer.展开更多
BACKGROUND Gastric cancer(GC)is prevalent and aggressive,especially when patients have distant lung metastases,which often places patients into advanced stages.By identifying prognostic variables for lung metastasis i...BACKGROUND Gastric cancer(GC)is prevalent and aggressive,especially when patients have distant lung metastases,which often places patients into advanced stages.By identifying prognostic variables for lung metastasis in GC patients,it may be po-ssible to construct a good prediction model for both overall survival(OS)and the cumulative incidence prediction(CIP)plot of the tumour.AIM To investigate the predictors of GC with lung metastasis(GCLM)to produce nomograms for OS and generate CIP by using cancer-specific survival(CSS)data.METHODS Data from January 2000 to December 2020 involving 1652 patients with GCLM were obtained from the Surveillance,epidemiology,and end results program database.The major observational endpoint was OS;hence,patients were se-parated into training and validation groups.Correlation analysis determined va-rious connections.Univariate and multivariate Cox analyses validated the independent predictive factors.Nomogram distinction and calibration were performed with the time-dependent area under the curve(AUC)and calibration curves.To evaluate the accuracy and clinical usefulness of the nomograms,decision curve analysis(DCA)was performed.The clinical utility of the novel prognostic model was compared to that of the 7th edition of the American Joint Committee on Cancer(AJCC)staging system by utilizing Net Reclassification Improvement(NRI)and Integrated Discrimination Improvement(IDI).Finally,the OS prognostic model and Cox-AJCC risk stratification model modified for the AJCC system were compared.RESULTS For the purpose of creating the OS nomogram,a CIP plot based on CSS was generated.Cox multivariate regression analysis identified eleven significant prognostic factors(P<0.05)related to liver metastasis,bone metastasis,primary site,surgery,regional surgery,treatment sequence,chemotherapy,radiotherapy,positive lymph node count,N staging,and time from diagnosis to treatment.It was clear from the DCA(net benefit>0),time-de-pendent ROC curve(training/validation set AUC>0.7),and calibration curve(reliability slope closer to 45 degrees)results that the OS nomogram demonstrated a high level of predictive efficiency.The OS prediction model(New Model AUC=0.83)also performed much better than the old Cox-AJCC model(AUC difference between the new model and the old model greater than 0)in terms of risk stratification(P<0.0001)and verification using the IDI and NRI.CONCLUSION The OS nomogram for GCLM successfully predicts 1-and 3-year OS.Moreover,this approach can help to ap-propriately classify patients into high-risk and low-risk groups,thereby guiding treatment.展开更多
BACKGROUND Breast cancer brain metastasis(BCBM)is an advanced breast disease that is difficult to treat and is associated with a high risk of death.Patient prognosis is usually poor,with reduced quality of life.In thi...BACKGROUND Breast cancer brain metastasis(BCBM)is an advanced breast disease that is difficult to treat and is associated with a high risk of death.Patient prognosis is usually poor,with reduced quality of life.In this context,we report the case of a patient with HER-2-positive BCBM treated with a macromolecular mAb(ine-tetamab)combined with a small molecule tyrosine kinase inhibitor(TKI).CASE SUMMARY The patient was a 58-year-old woman with a 12-year history of type 2 diabetes.She was compliant with regular insulin treatment and had good blood glucose control.The patient was diagnosed with invasive carcinoma of the right breast(T3N1M0 stage IIIa,HER2-positive type)through aspiration biopsy of the ipsilateral breast due to the discovery of a breast tumor in February 2019.Immunohistochemistry showed ER(-),PR(-),HER-2(3+),and Ki-67(55-60%+).Preoperative neoadjuvant chemotherapy,i.e.,the AC-TH regimen(epirubicin,cyclophosphamide,docetaxel-paclitaxel,and trastuzumab),was administered for 8 cycles.She underwent modified radical mastectomy of the right breast in November 2019 and received tocilizumab targeted therapy for 1 year.Brain metastasis was found 9 mo after surgery.She underwent brain metastasectomy in August 2020.Immunohistochemistry showed ER(-)and PR.(-),HER-2(3+),and Ki-67(10-20%+).In November 2020,the patient experienced headache symptoms.After an examination,tumor recurrence in the original surgical region of the brain was observed,and the patient was treated with inetetamab,pyrotinib,and capecitabine.Whole-brain radiotherapy was recommended.The patient and her family refused radiotherapy for personal reasons.In September 2021,a routine examination revealed that the brain tumor was considerably larger.The original systemic treatment was continued and combined with intensity-modulated radiation therapy for brain metastases,followed by regular hospitalization and routine examinations.The patient’s condition is generally stable,and she has a relatively high quality of life.This case report demonstrates that in patients with BCBM and resistance to trastuzumab,inetetamab combined with pyrotinib and chemotherapy can prolong survival.CONCLUSION Inetetamab combined with small molecule TKI drugs,chemotherapy and radiation may be an effective regimen for maintaining stable disease in patients with BCBM.展开更多
Autophagy is a "self-degradative" process and is involved in the maintenance of cellular homeostasis and the control of cellular components by facilitating the clearance or turnover of long-lived or misfolde...Autophagy is a "self-degradative" process and is involved in the maintenance of cellular homeostasis and the control of cellular components by facilitating the clearance or turnover of long-lived or misfolded proteins, protein aggregates, and damaged organelles. Autophagy plays a dual role in cancer, including in tumor progression and tumor promotion, suggesting that autophagy acts as a double-edged sword in cancer cells. Liver cancer is one of the greatest leading causes of cancer death worldwide due to its high recurrence rate and poor prognosis. Especially in China, liver cancer has become one of the most common cancers due to the high infection rate of hepatitis virus. In primary liver cancer, hepatocellular carcinoma (HCC) is the most common type. Considering the perniciousness and complexity of HCC, it is essential to elucidate the function of autophagy in HCC. In this review, we summarize the physiological function of autophagy in cancer, analyze the role of autophagy in tumorigenesis and metastasis, discuss the therapeutic strategies targeting autophagy and the mechanisms of drug-resistance in HCC, and provide potential methods to circumvent resistance and combined anticancer strategies for HCC patients.展开更多
The process of lymphatic metastasis was proved to be associated with podoplanin-expressing macrophages in breast cancer(BC).This study aimed to investigate the role of the M2 phenotype of tumor-associated macrophages ...The process of lymphatic metastasis was proved to be associated with podoplanin-expressing macrophages in breast cancer(BC).This study aimed to investigate the role of the M2 phenotype of tumor-associated macrophages and mine the key M2 macrophages-related genes for lymph node metastasis in BC.We downloaded the GSE158399 dataset from the Gene Expression Omnibus(GEO)database,which includes transcriptomic profiles of individual cells from primary tumors,negative lymph nodes(NLNs),and positive lymph nodes(PLNs)of breast cancer patients.The cell subsets were identified by clustering analysis after quality control of the scRNA-seq using Seurat.The activation and migration capability of M2 macrophages were evaluated with R package“GSVA”.The key M2 macrophages-related genes were screened from the differential expressed genes(DEGs)and M2 macrophages activation and migration gene sets collected from MSigDB database.Our analysis identified three main cell types in primary tumors,NLNs,and PLNs:basal cells,luminal cells,and immune cell subsets.The further cell type classification of immune cell subsets indicated M2 macrophages accumulation in NLs and PLs.The GSVA enrichment scores for activation and migration capability were increased significantly in M2 macrophages from primary tumors than NLNs and PLNs(pvalue<0.001).Seven M2 macrophages activation-related and 15 M2 macrophages migration-related genes were significantly up-regulated in primary tumors than NLNs and PLNs.The proportion and GSVA enrichment scores for activation and migration of M2 macrophages may be potential markers for lymph node metastasis in breast cancer.Our study demonstrated that twenty-two up-regulated mRNA may be possible therapeutic targets for lymph node metastasis in breast cancer.展开更多
BACKGROUND Superficial esophageal squamous cell carcinoma(ESCC)is defined as cancer infiltrating the mucosa and submucosa,regardless of regional lymph node metastasis(LNM).Endoscopic resection of superficial ESCC is s...BACKGROUND Superficial esophageal squamous cell carcinoma(ESCC)is defined as cancer infiltrating the mucosa and submucosa,regardless of regional lymph node metastasis(LNM).Endoscopic resection of superficial ESCC is suitable for lesions that have no or low risk of LNM.Patients with a high risk of LNM always need further treatment after endoscopic resection.Therefore,accurately assessing the risk of LNM is critical for additional treatment options.AIM To analyze risk factors for LNM and develop a nomogram to predict LNM risk in superficial ESCC patients.METHODS Clinical and pathological data of superficial ESCC patients undergoing esophagectomy from January 1,2009 to January 31,2016 were collected.Logistic regression analysis was used to predict LNM risk factors,and a nomogram was developed based on risk factors derived from multivariate logistic regression analysis.The receiver operating characteristic(ROC)curve was used to obtain the accuracy of the nomogram model.RESULTSA total of 4660 patients with esophageal cancer underwent esophagectomy.Of these,474 superficial ESCC patientswere enrolled in the final analysis,with 322 patients in the training set and 142 patients in the validation set.Theprevalence of LNM was 3.29%(5/152)for intramucosal cancer and increased to 26.40%(85/322)for submucosalcancer.Multivariate logistic analysis showed that tumor size,invasive depth,tumor differentiation,infiltrativegrowth pattern,tumor budding,and lymphovascular invasion were significantly correlated with LNM.Anomogram using these six variables showed good discrimination with an area under the ROC curve of 0.789(95%CI:0.737-0.841)in the training set and 0.827(95%CI:0.755-0.899)in the validation set.CONCLUSIONWe developed a useful nomogram model to predict LNM risk for superficial ESCC patients which will facilitateadditional decision-making in treating patients who undergo endoscopic resection.展开更多
BACKGROUND Breast cancer(BC)has become the most common malignancy in women.The incidence and detection rates of BC brain metastasis(BCBM)have increased with the progress of imaging,multidisciplinary treatment techniqu...BACKGROUND Breast cancer(BC)has become the most common malignancy in women.The incidence and detection rates of BC brain metastasis(BCBM)have increased with the progress of imaging,multidisciplinary treatment techniques and the extension of survival time of BC patients.BM seriously affects the quality of life and survival prognosis of BC patients.Therefore,clinical research on the clinicopathological features and prognostic factors of BCBM is valuable.By analyzing the clinicopathological parameters of BCBM patients,and assessing the risk factors and prognostic indicators,we can perform hierarchical diagnosis and treatment on the high-risk population of BCBM,and achieve clinical benefits of early diagnosis and treatment.AIM To explore the clinicopathological features and prognostic factors of BCBM,and provide references for diagnosis,treatment and management of BCBM.METHODS The clinicopathological data of 68 BCBM patients admitted to the Air Force Medical Center,Chinese People’s Liberation Army(formerly Air Force General Hospital)from 2000 to 2022 were collected.Another 136 BC patients without BM were matched at a ratio of 1:2 based on the age and site of onset for retrospective analysis.Categorical data were subjected to χ^(2) test or Fisher’s exact probability test,and the variables with P<0.05 in the univariate Cox proportional hazards model were incorporated into the multivariate model to identify high-risk factors and independent prognostic factors of BCBM,with a hazard ratio(HR)>1 suggesting poor prognostic factors.The survival time of patients was estimated by the Kaplan-Meier method,and overall survival was compared between groups by log-rank test.RESULTS Multivariate Cox regression analysis showed that patients with stage Ⅲ/Ⅳ tumor at initial diagnosis[HR:5.58,95% confidence interval(CI):1.99–15.68],lung metastasis(HR:24.18,95%CI:6.40-91.43),human epidermal growth factor receptor 2(HER2)-overexpressing BC and triple-negative BC were more prone to BM.As can be seen from the prognostic data,52 of the 68 BCBM patients had died by the end of follow-up,and the median time from diagnosis of BC to the occurrence of BM and from the occurrence of BM to death or last follow-up was 33.5 and 14 mo,respectively.It was confirmed by multivariate Cox regression analysis that patients with neurological symptoms(HR:1.923,95%CI:1.005-3.680),with bone metastasis(HR:2.011,95%CI:1.056-3.831),and BM of HER2-overexpressing and triple-negative BC had shorter survival time.CONCLUSION HER2-overexpressing,triple-negative BC,late tumor stage and lung metastasis are risk factors of BM.The presence of neurological symptoms,bone metastasis,and molecular type are influencing prognosis factors of BCBM.展开更多
Introduction The dissemination of cancer cells to organs initiates the formation of an aggressive cancer phenotype and is a predominant cause of cancer-associated death.For most epithelial cancers,lymphatic system met...Introduction The dissemination of cancer cells to organs initiates the formation of an aggressive cancer phenotype and is a predominant cause of cancer-associated death.For most epithelial cancers,lymphatic system metastasis has been characterized as the most common and earliest metastatic pathway,and the detection of metastasis in lymph nodes(LNs)often predicts poor survival among patients'.Although increasing attention is being paid to the clinical importance of LN metastasis,the underlying mechanisms have remained unclear in the past decade.Accumulating evidence suggests that the occurrence of LN metastasis is not stochastic but is a programming biological event regulated by the bidirectional crosstalk between metastasis-initiating cancer cells and the tumor microenvironment(TME)2.However,the regulators and patterns of cancer-TME communication in LN metastasis remain to be furtherexplored.展开更多
Current colorectal cancer (CRC) treatments exhibit unwanted cytotoxicity against healthy proliferating cells. Hence, these therapeutics demand higher specificity upon drug delivery, a task that may be facilitated by t...Current colorectal cancer (CRC) treatments exhibit unwanted cytotoxicity against healthy proliferating cells. Hence, these therapeutics demand higher specificity upon drug delivery, a task that may be facilitated by the discovery of anticancer agents bearing critical mechanisms of action. Baicalein is a flavonoid with promising anticancer activity, among other pharmacological benefits, and has therefore been of high clinical interest. We tested baicalein in vitro for its effect on several CRC hallmarks, including the suppression of metastasis (the spread of cancer cells from their initial site), the ability to induce apoptosis (cell death), and the inhibition of proliferation (the growth of cells). The suppression of the metastasis of CRC cells was recorded via two studies: the cell migration assay and the in silico docking of baicalein with toll-like receptor 4 (TLR4) and matrix metalloproteinase-9 (MMP-9). Results from the cell migration assay showed that baicalein inhibited metastasis by up to 25.76% (p 0.01) in a concentration-dependent manner. We then reinforced these results by docking baicalein with TLR4 (binding affinity: -8.4 kcal/mol) and docking baicalein with MMP-9 (binding affinity: -7.9 kcal/mol), classifying strong binding affinities as those less than -6.0 kcal/mol. The induction of cell death was measured using a caspase activity assay. Again, a docking study was done to reinforce the findings from the primary in vitro experiment, though this time between baicalein and caspase-3 (binding affinity: -7.1 kcal/mol). Despite mixed observations in concentration dependence, caspase activity, relative to control, reached a maximal increase of 88.6% (p 0.01), and results from the MTT assay demonstrated a survival rate, relative to control, of as low as 59.64%. Considerations for future studies include the testing of baicalein in vivo and on more aberrative CRC cell lines.展开更多
基金Supported by Research Grants Council of the Hong Kong SAR,China,General Research Fund,No.17111917.
文摘Esophageal squamous cell carcinoma(ESCC)is the major subtype of esophageal cancer that is prevalent in Eastern Asia.Despite recent advances in therapy,the outcome of ESCC patients is still dismal.MicroRNAs(miRNAs)are non-coding RNAs which can negatively modulate gene expression at the post-transcriptional level.The involvement and roles of miRNAs have become one of the hot topics of cancer research in recent years.In ESCC,genetic variations within miRNA coding genes were found to have distinct epidemiological significance in different populations.Dysregulated expression of several miRNAs was reported to be associated with therapeutic response.Functionally,miRNAs can act either in an oncogenic or a tumor-suppressive manner during tumorigenesis of ESCC by interrupting signaling pathways associated with cell proliferation,metabolism,cancer stemness,and resistance to chemo-or radiotherapy.Moreover,miRNAs modulate metastasis of ESCC by targeting genes that regulate cytoskeleton dynamics,extracellular matrix remodeling,epithelial-mesenchymal transition,and tumor microenvironment.Most importantly,mounting evidence suggests that inhibiting oncogenic miRNAs or restoring the loss of tumor-suppressive miRNAs has therapeutic potential in the treatment of ESCC.Here,we review and discuss recent studies on the significance,biological functions,and therapeutic potential of miRNAs in tumorigenesis and metastasis of ESCC.
文摘Dysregulation of polycomb group protein Bmi-1 expression has been linked with an invasive phenotype of certain human cancers and poor prognosis of patients; however, the underlying mechanisms are
基金supported by National Natural Science Foundation of China [Grant numbers: 82272868 and 82173180]the Foundation of Joint Funds for the Innovation of Science and Technology, Fujian Province (No. 2020Y9126)Fujian Provincial Health Technology Project [Grant number: 2020CXA049]。
文摘Wnt signaling are critical pathway involved in organ development, tumorigenesis, and cancer progression. WNT7A, a member of the Wnt family, remains poorly understood in terms of its role and the underlying molecular mechanisms it entails in head and neck squamous cell carcinoma (HNSCC). According to the Cancer Genome Atlas (TCGA), transcriptome sequencing data of HNSCC, the expression level of WNT7A in tumors was found to be higher than in adjacent normal tissues, which was validated using Real-time RT-PCR and immunohistochemistry. Unexpectedly, overexpression of WNT7A did not activate the canonical Wnt-β-catenin pathway in HNSCC. Instead, our findings suggested that WNT7A potentially activated the FZD7/JAK1/STAT3 signaling pathway, leading to enhanced cell proliferation, self-renewal, and resistance to apoptosis. Furthermore, in a patient-derived xenograft (PDX) tumor model, high expression of WNT7A and phosphorylated STAT3 was observed, which positively correlated with tumor progression.These findings underscore the significance of WNT7A in HNSCC progression and propose the targeting of key molecules within the FZD7/JAK1/STAT3 pathway as a promising strategy for precise treatment of HNSCC.
基金supported by the National Natural Science Foundation of China(Grant No.82173601)Yili&Jiangsu Joint Institute of Health(Grant No.yl2021ms02).
文摘The interplay between DNA replication stress and immune microenvironment alterations is known to play a crucial role in colorectal tumorigenesis,but a comprehensive understanding of their association with and relevant biomarkers involved in colorectal tumorigenesis is lacking.To address this gap,we conducted a study aiming to investigate this association and identify relevant biomarkers.We analyzed transcriptomic and proteomic profiles of 904 colorectal tumor tissues and 342 normal tissues to examine pathway enrichment,biological activity,and the immune microenvironment.Additionally,we evaluated genetic effects of single variants and genes on colorectal cancer susceptibility using data from genome-wide association studies(GWASs)involving both East Asian(7062 cases and 195745 controls)and European(24476 cases and 23073 controls)populations.We employed mediation analysis to infer the causal pathway,and applied multiplex immunofluorescence to visualize colocalized biomarkers in colorectal tumors and immune cells.Our findings revealed that both DNA replication activity and the flap structure-specific endonuclease 1(FEN1)gene were significantly enriched in colorectal tumor tissues,compared with normal tissues.Moreover,a genetic variant rs4246215 G>T in FEN1 was associated with a decreased risk of colorectal cancer(odds ratio=0.94,95%confidence interval:0.90–0.97,P_(meta)=4.70×10^(-9)).Importantly,we identified basophils and eosinophils that both exhibited a significantly decreased infiltration in colorectal tumors,and were regulated by rs4246215 through causal pathways involving both FEN1 and DNA replication.In conclusion,this trans-omics incorporating GWAS data provides insights into a plausible pathway connecting DNA replication and immunity,expanding biological knowledge of colorectal tumorigenesis and therapeutic targets.
文摘Greenblatt and his team have unveiled vertebral skeletal stem cells(vSSCs)as a critical player in the landscape of bone metastasis.This commentary delves into the transformative discoveries surrounding vSSCs,emphasizing their distinct role in bone metastasis compared to other stem cell lineages.We illuminate the unique properties and functions of vSSCs,which may account for the elevated susceptibility of vertebral bones to metastatic invasion.Furthermore,we explore the exciting therapeutic horizons opened by this newfound understanding.These include potential interventions targeting vSSCs,modulation of associated signaling pathways,and broader implications for the treatment and management of bone metastasis.By shedding light on these game-changing insights,we hope to pave the way for novel strategies that could revolutionize the prognosis and treatment landscape for cancer patients with metastatic bone disease.
文摘Objective:To explore the regulatory mechanism of NUDT5 in glioblastoma multiforme(GBM).Methods:GEPIA database was used to predict the expressions of NUDT5 and tripartite motif family proteins 47(TRIM47)in GBM patients.RT-qPCR and Western blot analyses were performed to examine NUDT5 expression in GBM cells.LN-229 cell proliferation,migration as well as invasion were estimated by CCK-8,colony formation,wound healing,and Transwell assays following interference with NUDT5.ECAR assay,L-lactic acid kit,glucose detection kit,and ATP detection kit were applied for the detection of glycolysis-related indexes.Co-immunoprecipitation experiment was carried out to verify the relationship between NUDT5 and TRIM47.Results:GEPIA database showed that NUDT5 expression was significantly increased in GBM patients.Inhibiting the expression of NUDT5 in GBM cells significantly suppressed the viability,proliferation,invasion,migration,and glycolysis of GBM cells.Moreover,TRIM47 was highly expressed in GBM cells and interacted with NUDT5.Overexpression of TRIM47 partially reversed the inhibitory effect of NUDT5 downregulation on the proliferation,metastasis,and glycolysis of GBM cells.Conclusions:NUDT5 promotes the growth,metastasis,and Warburg effect of GBM cells by upregulating TRIM47.Both NUDT5 and TRIM47 can be used as targets for GMB treatment.
基金Supported by State Administration of Traditional Chinese Medicine Base Construction Stomach Cancer Special Fund,No.Y2020CX57Jiangsu Provincial Graduate Research and Practical Innovation Program Project,No.SJCX23-0799.
文摘BACKGROUND Duodenal cancer is one of the most common subtypes of small intestinal cancer,and distant metastasis(DM)in this type of cancer still leads to poor prognosis.Although nomograms have recently been used in tumor areas,no studies have focused on the diagnostic and prognostic evaluation of DM in patients with primary duodenal cancer.AIM To develop and evaluate nomograms for predicting the risk of DM and person-alized prognosis in patients with duodenal cancer.METHODS Data on duodenal cancer patients diagnosed between 2010 and 2019 were extracted from the Surveillance,Epidemiology,and End Results database.Univariate and multivariate logistic regression analyses were used to identify independent risk factors for DM in patients with duodenal cancer,and univariate and multivariate Cox proportional hazards regression analyses were used to determine independent prognostic factors in duodenal cancer patients with DM.Two novel nomograms were established,and the results were evaluated by receiver operating characteristic(ROC)curves,calibration curves,and decision curve analysis(DCA).RESULTS A total of 2603 patients with duodenal cancer were included,of whom 457 cases(17.56%)had DM at the time of diagnosis.Logistic analysis revealed independent risk factors for DM in duodenal cancer patients,including gender,grade,tumor size,T stage,and N stage(P<0.05).Univariate and multivariate COX analyses further identified independent prognostic factors for duodenal cancer patients with DM,including age,histological type,T stage,tumor grade,tumor size,bone metastasis,chemotherapy,and surgery(P<0.05).The accuracy of the nomograms was validated in the training set,validation set,and expanded testing set using ROC curves,calibration curves,and DCA curves.The results of Kaplan-Meier survival curves(P<0.001)indicated that both nomograms accurately predicted the occurrence and prognosis of DM in patients with duodenal cancer.CONCLUSION The two nomograms are expected as effective tools for predicting DM risk in duodenal cancer patients and offering personalized prognosis predictions for those with DM,potentially enhancing clinical decision-making.
文摘BACKGROUND Metastatic cardiac tumors are known to occur more frequently than primary cardiac tumors,however,they often remain asymptomatic and are commonly dis-covered on autopsy.Malignant tumors with a relatively high frequency of cardiac metastasis include mesothelioma,melanoma,lung cancer,and breast cancer,whereas reports of esophageal cancer with cardiac metastasis are rare.CASE SUMMARY The case of a 60-year-old man who complained of dysphagia is presented.Upper gastrointestinal endoscopy showed a submucosal tumor-like elevated lesion in the esophagus causing stenosis.Contrast-enhanced computed tomography showed left atrial compression due to the esophageal tumor,multiple liver and lung metastases,and a left pleural effusion.Pathological examination of a biopsy speci-men from the esophageal tumor showed spindle-shaped cells,raising suspicion of esophageal sarcoma.The disease progressed rapidly,and systemic chemotherapy was deemed necessary,however,due to his poor general condition,adminis-tration of cytotoxic agents was considered difficult.Given his high Combined Positive Score,nivolumab was administered,however,the patient soon died from the disease.The autopsy confirmed spindle cell carcinoma(SCC)of the esophagus and cardiac metastasis with similar histological features.Cancer stem cell markers,ZEB1 and TWIST,were positive in both the primary tumor and the cardiac metastasis.CONCLUSION To the best of our knowledge,there have been no prior reports of cardiac metastasis of esophageal SCC.This case highlights our experience with a patient with esophageal SCC who progressed rapidly and died from the disease,with the autopsy examination showing cardiac metastasis.
基金Supported by National Natural Foundation of China,No.821742232019 Chinese and Western Medicine Clinical Collaborative Capacity Building Project for Major Difficult Diseases,No.2019-ZX-005。
文摘BACKGROUND Esophageal squamous cell carcinoma(ESCC)is one of the most common malignancies worldwide,and its development comprises a multistep process from intraepithelial neoplasia(IN)to carcinoma(CA).However,the critical regulators and underlying molecular mechanisms remain largely unknown.AIM To explore the genes and infiltrating immune cells in the microenvironment that are associated with the multistage progression of ESCC to facilitate diagnosis and early intervention.METHODS A mouse model mimicking the multistage development of ESCC was established by providing warter containing 4-nitroquinoline 1-oxide(4NQO)to C57BL/6 mice.Moreover,we established a control group without 4NQO treatment of mice.Then,transcriptome sequencing was performed for esophageal tissues from patients with different pathological statuses,including low-grade IN(LGIN),high-grade IN(HGIN),and CA,and controlled normal tissue(NOR)samples.Differentially expressed genes(DEGs)were identified in the LGIN,HGIN,and CA groups,and the biological functions of the DEGs were analyzed via Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses.The CIBERSORT algorithm was used to detect the pattern of immune cell infilt-ration.Immunohistochemistry(IHC)was also conducted to validate our results.Finally,the Luminex multiplex cytokine analysis was utilized to measure the serum cytokine levels in the mice.RESULTS Compared with those in the NOR group,a total of 681541,and 840 DEGs were obtained in the LGIN,HGIN,and CA groups,respectively.Using the intersection of the three sets of DEGs,we identified 86 genes as key genes involved in the development of ESCC.Enrichment analysis revealed that these genes were enriched mainly in the keratinization,epidermal cell differentiation,and interleukin(IL)-17 signaling pathways.CIBERSORT analysis revealed that,compared with those in the NOR group,M0 and M1 macrophages in the 4NQO group showed stronger infiltration,which was validated by IHC.Serum cytokine analysis revealed that,compared with those in the NOR group,IL-1βand IL-6 were upregulated,while IL-10 was downregulated in the LGIN,HGIN,and CA groups.Moreover,the expression of the representative key genes,such as S100a8 and Krt6b,was verified in external human samples,and the results of immunohistochemical staining were consistent with the findings in mice.CONCLUSION We identified a set of key genes represented by S100a8 and Krt6b and investigated their potential biological functions.In addition,we found that macrophage infiltration and abnormal alterations in the levels of inflam-mation-associated cytokines,such as IL-1β,IL-6,and IL-10,in the peripheral blood may be closely associated with the development of ESCC.
文摘Colorectal cancer liver metastasis(CRLM)presents a clinical challenge,and optimizing treatment strategies is crucial for improving patient outcomes.Surgical resection,a key element in achieving prolonged survival,is often linked to a heightened risk of recurrence.Acknowledging the potential benefits of preoperative neoadjuvant chemotherapy in managing resectable liver metastases,this approach has gained attention for its role in tumor downsizing,assessing biological behavior,and reducing the risk of postoperative recurrence.However,the use of neoadjuvant chemotherapy in initially resectable CRLM sparks ongoing debates.The balance between tumor reduction and the risk of hepatic injury,coupled with concerns about delaying surgery,necessitates a nuanced approach.This article explores recent research insights and draws upon the practical experiences at our center to address critical issues regarding considerations for initially resectable cases.Examining the criteria for patient selection and the judicious choice of neoadjuvant regimens are pivotal areas of discussion.Striking the right balance between maximizing treatment efficacy and minimizing adverse effects is imperative.The dynamic landscape of precision medicine is also reflected in the evolving role of gene testing,such as RAS/BRAF and PIK3CA,in tailoring neoadjuvant regimens.Furthermore,the review emphasizes the need for a multidisciplinary approach to navigate the comp-lexities of CRLM.Integrating technical expertise and biological insights is crucial in refining neoadjuvant strategies.The management of progression following neoadjuvant chemotherapy requires a tailored approach,acknowledging the diverse biological behaviors that may emerge.In conclusion,this review aims to provide a comprehensive perspective on the considerations,challenges,and advancements in the use of neoadjuvant chemotherapy for initially resectable CRLM.By combining evidencebased insights with practical experiences,we aspire to contribute to the ongoing discourse on refining treatment paradigms for improved outcomes in patients with CRLM.
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Hainan Clinical Medical Center Construction Project(2021)Excellent Talent Team of Hainan Province(No.QRCBT202121)Key R&D Program of Hainan Province(No.ZDYF2022SHFZ109)。
文摘Objective:The aim was to analyse the clinical features of leptomeningeal metastasis with banded high signal in the brainstem.Methods:In this paper,we report two cases of lung adenocarcinoma with soft meningeal metastasis,collected from the First Affiliated Hospital of Hainan Medical College,and searched the databases of CNKI,Wanfang,VIP,PubMed,Web of Science,and other databases which reported the MRI manifestation of"brainstem bandlike high signal",and collected the patients'past medical history,symptoms,signs,genetic findings,cerebrospinal fluid manifestation,treatment,and prognosis.Result:A total of 28 patients were included,of whom 26 had a history of lung adenocarcinoma and 2 were found to have occupational changes in the lungs.Magnetic resonance imaging(MRI)showed a band-like high signal in the ventral part of the brainstem on T2-FLAIR,symmetrical on both sides,which could extend to the cerebellar peduncles,with high signals on diffusion-weighted imaging(DWI),low signals on apparent diffusion coefficient(ADC),and long T1 signals on T1-weighted imaging,long T2 signals on T2 weighted imaging,and no long T2 signals on enhancement scan.T1-weighted imaging was a long T1 signal,T2-weighted imaging was a long T2 signal,and no enhancement was seen on enhanced scanning.Conclusion:It is important to recognize leptomeningeal metastasis of lung cancer,and the non-enhancing band of high signal in the brainstem on T2-FLAIR and DWI is likely to be the characteristic manifestation of leptomeningeal metastasis of non-small cell lung cancer.
基金Supported by Peng-Cheng Talent-Medical Young Reserve Talent Training Program,No.XWRCHT20220002Xuzhou City Health and Health Commission Technology Project Contract,No.XWKYHT20230081and Key Research and Development Plan Project of Xuzhou City,No.KC22179.
文摘BACKGROUND Gastric cancer(GC)is prevalent and aggressive,especially when patients have distant lung metastases,which often places patients into advanced stages.By identifying prognostic variables for lung metastasis in GC patients,it may be po-ssible to construct a good prediction model for both overall survival(OS)and the cumulative incidence prediction(CIP)plot of the tumour.AIM To investigate the predictors of GC with lung metastasis(GCLM)to produce nomograms for OS and generate CIP by using cancer-specific survival(CSS)data.METHODS Data from January 2000 to December 2020 involving 1652 patients with GCLM were obtained from the Surveillance,epidemiology,and end results program database.The major observational endpoint was OS;hence,patients were se-parated into training and validation groups.Correlation analysis determined va-rious connections.Univariate and multivariate Cox analyses validated the independent predictive factors.Nomogram distinction and calibration were performed with the time-dependent area under the curve(AUC)and calibration curves.To evaluate the accuracy and clinical usefulness of the nomograms,decision curve analysis(DCA)was performed.The clinical utility of the novel prognostic model was compared to that of the 7th edition of the American Joint Committee on Cancer(AJCC)staging system by utilizing Net Reclassification Improvement(NRI)and Integrated Discrimination Improvement(IDI).Finally,the OS prognostic model and Cox-AJCC risk stratification model modified for the AJCC system were compared.RESULTS For the purpose of creating the OS nomogram,a CIP plot based on CSS was generated.Cox multivariate regression analysis identified eleven significant prognostic factors(P<0.05)related to liver metastasis,bone metastasis,primary site,surgery,regional surgery,treatment sequence,chemotherapy,radiotherapy,positive lymph node count,N staging,and time from diagnosis to treatment.It was clear from the DCA(net benefit>0),time-de-pendent ROC curve(training/validation set AUC>0.7),and calibration curve(reliability slope closer to 45 degrees)results that the OS nomogram demonstrated a high level of predictive efficiency.The OS prediction model(New Model AUC=0.83)also performed much better than the old Cox-AJCC model(AUC difference between the new model and the old model greater than 0)in terms of risk stratification(P<0.0001)and verification using the IDI and NRI.CONCLUSION The OS nomogram for GCLM successfully predicts 1-and 3-year OS.Moreover,this approach can help to ap-propriately classify patients into high-risk and low-risk groups,thereby guiding treatment.
文摘BACKGROUND Breast cancer brain metastasis(BCBM)is an advanced breast disease that is difficult to treat and is associated with a high risk of death.Patient prognosis is usually poor,with reduced quality of life.In this context,we report the case of a patient with HER-2-positive BCBM treated with a macromolecular mAb(ine-tetamab)combined with a small molecule tyrosine kinase inhibitor(TKI).CASE SUMMARY The patient was a 58-year-old woman with a 12-year history of type 2 diabetes.She was compliant with regular insulin treatment and had good blood glucose control.The patient was diagnosed with invasive carcinoma of the right breast(T3N1M0 stage IIIa,HER2-positive type)through aspiration biopsy of the ipsilateral breast due to the discovery of a breast tumor in February 2019.Immunohistochemistry showed ER(-),PR(-),HER-2(3+),and Ki-67(55-60%+).Preoperative neoadjuvant chemotherapy,i.e.,the AC-TH regimen(epirubicin,cyclophosphamide,docetaxel-paclitaxel,and trastuzumab),was administered for 8 cycles.She underwent modified radical mastectomy of the right breast in November 2019 and received tocilizumab targeted therapy for 1 year.Brain metastasis was found 9 mo after surgery.She underwent brain metastasectomy in August 2020.Immunohistochemistry showed ER(-)and PR.(-),HER-2(3+),and Ki-67(10-20%+).In November 2020,the patient experienced headache symptoms.After an examination,tumor recurrence in the original surgical region of the brain was observed,and the patient was treated with inetetamab,pyrotinib,and capecitabine.Whole-brain radiotherapy was recommended.The patient and her family refused radiotherapy for personal reasons.In September 2021,a routine examination revealed that the brain tumor was considerably larger.The original systemic treatment was continued and combined with intensity-modulated radiation therapy for brain metastases,followed by regular hospitalization and routine examinations.The patient’s condition is generally stable,and she has a relatively high quality of life.This case report demonstrates that in patients with BCBM and resistance to trastuzumab,inetetamab combined with pyrotinib and chemotherapy can prolong survival.CONCLUSION Inetetamab combined with small molecule TKI drugs,chemotherapy and radiation may be an effective regimen for maintaining stable disease in patients with BCBM.
基金Supported by Natural Science Foundation of China,No.81803069Natural Science Foundation of Zhejiang Province of China,No.LY18C070002 and No.LY16H160056521 Talent Project of Zhejiang Sci-Tech University
文摘Autophagy is a "self-degradative" process and is involved in the maintenance of cellular homeostasis and the control of cellular components by facilitating the clearance or turnover of long-lived or misfolded proteins, protein aggregates, and damaged organelles. Autophagy plays a dual role in cancer, including in tumor progression and tumor promotion, suggesting that autophagy acts as a double-edged sword in cancer cells. Liver cancer is one of the greatest leading causes of cancer death worldwide due to its high recurrence rate and poor prognosis. Especially in China, liver cancer has become one of the most common cancers due to the high infection rate of hepatitis virus. In primary liver cancer, hepatocellular carcinoma (HCC) is the most common type. Considering the perniciousness and complexity of HCC, it is essential to elucidate the function of autophagy in HCC. In this review, we summarize the physiological function of autophagy in cancer, analyze the role of autophagy in tumorigenesis and metastasis, discuss the therapeutic strategies targeting autophagy and the mechanisms of drug-resistance in HCC, and provide potential methods to circumvent resistance and combined anticancer strategies for HCC patients.
文摘The process of lymphatic metastasis was proved to be associated with podoplanin-expressing macrophages in breast cancer(BC).This study aimed to investigate the role of the M2 phenotype of tumor-associated macrophages and mine the key M2 macrophages-related genes for lymph node metastasis in BC.We downloaded the GSE158399 dataset from the Gene Expression Omnibus(GEO)database,which includes transcriptomic profiles of individual cells from primary tumors,negative lymph nodes(NLNs),and positive lymph nodes(PLNs)of breast cancer patients.The cell subsets were identified by clustering analysis after quality control of the scRNA-seq using Seurat.The activation and migration capability of M2 macrophages were evaluated with R package“GSVA”.The key M2 macrophages-related genes were screened from the differential expressed genes(DEGs)and M2 macrophages activation and migration gene sets collected from MSigDB database.Our analysis identified three main cell types in primary tumors,NLNs,and PLNs:basal cells,luminal cells,and immune cell subsets.The further cell type classification of immune cell subsets indicated M2 macrophages accumulation in NLs and PLs.The GSVA enrichment scores for activation and migration capability were increased significantly in M2 macrophages from primary tumors than NLNs and PLNs(pvalue<0.001).Seven M2 macrophages activation-related and 15 M2 macrophages migration-related genes were significantly up-regulated in primary tumors than NLNs and PLNs.The proportion and GSVA enrichment scores for activation and migration of M2 macrophages may be potential markers for lymph node metastasis in breast cancer.Our study demonstrated that twenty-two up-regulated mRNA may be possible therapeutic targets for lymph node metastasis in breast cancer.
基金the National Natural Science Foundation of China,No.82173253the Sichuan Province Science and Technology Support Program,No.2022YFH0003 and No.2023NSFSC1900+1 种基金the Postdoctoral Research Foundation of West China Hospital,No.2021HXBH020and the Medico-Engineering Cooperation Funds from the University of Electronic Science and Technology of China and West China Hospital of Sichuan University,No.HXDZ22005.
文摘BACKGROUND Superficial esophageal squamous cell carcinoma(ESCC)is defined as cancer infiltrating the mucosa and submucosa,regardless of regional lymph node metastasis(LNM).Endoscopic resection of superficial ESCC is suitable for lesions that have no or low risk of LNM.Patients with a high risk of LNM always need further treatment after endoscopic resection.Therefore,accurately assessing the risk of LNM is critical for additional treatment options.AIM To analyze risk factors for LNM and develop a nomogram to predict LNM risk in superficial ESCC patients.METHODS Clinical and pathological data of superficial ESCC patients undergoing esophagectomy from January 1,2009 to January 31,2016 were collected.Logistic regression analysis was used to predict LNM risk factors,and a nomogram was developed based on risk factors derived from multivariate logistic regression analysis.The receiver operating characteristic(ROC)curve was used to obtain the accuracy of the nomogram model.RESULTSA total of 4660 patients with esophageal cancer underwent esophagectomy.Of these,474 superficial ESCC patientswere enrolled in the final analysis,with 322 patients in the training set and 142 patients in the validation set.Theprevalence of LNM was 3.29%(5/152)for intramucosal cancer and increased to 26.40%(85/322)for submucosalcancer.Multivariate logistic analysis showed that tumor size,invasive depth,tumor differentiation,infiltrativegrowth pattern,tumor budding,and lymphovascular invasion were significantly correlated with LNM.Anomogram using these six variables showed good discrimination with an area under the ROC curve of 0.789(95%CI:0.737-0.841)in the training set and 0.827(95%CI:0.755-0.899)in the validation set.CONCLUSIONWe developed a useful nomogram model to predict LNM risk for superficial ESCC patients which will facilitateadditional decision-making in treating patients who undergo endoscopic resection.
基金Supported by Outstanding Young Talents Program of Air Force Medical Center,PLA,No.22BJQN004Clinical Program of Air Force Medical University,No.Xiaoke2022-07.
文摘BACKGROUND Breast cancer(BC)has become the most common malignancy in women.The incidence and detection rates of BC brain metastasis(BCBM)have increased with the progress of imaging,multidisciplinary treatment techniques and the extension of survival time of BC patients.BM seriously affects the quality of life and survival prognosis of BC patients.Therefore,clinical research on the clinicopathological features and prognostic factors of BCBM is valuable.By analyzing the clinicopathological parameters of BCBM patients,and assessing the risk factors and prognostic indicators,we can perform hierarchical diagnosis and treatment on the high-risk population of BCBM,and achieve clinical benefits of early diagnosis and treatment.AIM To explore the clinicopathological features and prognostic factors of BCBM,and provide references for diagnosis,treatment and management of BCBM.METHODS The clinicopathological data of 68 BCBM patients admitted to the Air Force Medical Center,Chinese People’s Liberation Army(formerly Air Force General Hospital)from 2000 to 2022 were collected.Another 136 BC patients without BM were matched at a ratio of 1:2 based on the age and site of onset for retrospective analysis.Categorical data were subjected to χ^(2) test or Fisher’s exact probability test,and the variables with P<0.05 in the univariate Cox proportional hazards model were incorporated into the multivariate model to identify high-risk factors and independent prognostic factors of BCBM,with a hazard ratio(HR)>1 suggesting poor prognostic factors.The survival time of patients was estimated by the Kaplan-Meier method,and overall survival was compared between groups by log-rank test.RESULTS Multivariate Cox regression analysis showed that patients with stage Ⅲ/Ⅳ tumor at initial diagnosis[HR:5.58,95% confidence interval(CI):1.99–15.68],lung metastasis(HR:24.18,95%CI:6.40-91.43),human epidermal growth factor receptor 2(HER2)-overexpressing BC and triple-negative BC were more prone to BM.As can be seen from the prognostic data,52 of the 68 BCBM patients had died by the end of follow-up,and the median time from diagnosis of BC to the occurrence of BM and from the occurrence of BM to death or last follow-up was 33.5 and 14 mo,respectively.It was confirmed by multivariate Cox regression analysis that patients with neurological symptoms(HR:1.923,95%CI:1.005-3.680),with bone metastasis(HR:2.011,95%CI:1.056-3.831),and BM of HER2-overexpressing and triple-negative BC had shorter survival time.CONCLUSION HER2-overexpressing,triple-negative BC,late tumor stage and lung metastasis are risk factors of BM.The presence of neurological symptoms,bone metastasis,and molecular type are influencing prognosis factors of BCBM.
基金supported by grants from the National Key Research and Development Program of China(Grant No.2022YFA1305500)the National Natural Science Foundation of China(Grant Nos.82173272,82103536,81871945,and 81902589)+1 种基金the Guangdong Science and Technology Department(Grant Nos.2022B1515120086,and 2021B1515020091)the Science and Technology Program of Guangzhou(Grant Nos.202002030388,2022A1515012288,and 2021A1515010355)。
文摘Introduction The dissemination of cancer cells to organs initiates the formation of an aggressive cancer phenotype and is a predominant cause of cancer-associated death.For most epithelial cancers,lymphatic system metastasis has been characterized as the most common and earliest metastatic pathway,and the detection of metastasis in lymph nodes(LNs)often predicts poor survival among patients'.Although increasing attention is being paid to the clinical importance of LN metastasis,the underlying mechanisms have remained unclear in the past decade.Accumulating evidence suggests that the occurrence of LN metastasis is not stochastic but is a programming biological event regulated by the bidirectional crosstalk between metastasis-initiating cancer cells and the tumor microenvironment(TME)2.However,the regulators and patterns of cancer-TME communication in LN metastasis remain to be furtherexplored.
文摘Current colorectal cancer (CRC) treatments exhibit unwanted cytotoxicity against healthy proliferating cells. Hence, these therapeutics demand higher specificity upon drug delivery, a task that may be facilitated by the discovery of anticancer agents bearing critical mechanisms of action. Baicalein is a flavonoid with promising anticancer activity, among other pharmacological benefits, and has therefore been of high clinical interest. We tested baicalein in vitro for its effect on several CRC hallmarks, including the suppression of metastasis (the spread of cancer cells from their initial site), the ability to induce apoptosis (cell death), and the inhibition of proliferation (the growth of cells). The suppression of the metastasis of CRC cells was recorded via two studies: the cell migration assay and the in silico docking of baicalein with toll-like receptor 4 (TLR4) and matrix metalloproteinase-9 (MMP-9). Results from the cell migration assay showed that baicalein inhibited metastasis by up to 25.76% (p 0.01) in a concentration-dependent manner. We then reinforced these results by docking baicalein with TLR4 (binding affinity: -8.4 kcal/mol) and docking baicalein with MMP-9 (binding affinity: -7.9 kcal/mol), classifying strong binding affinities as those less than -6.0 kcal/mol. The induction of cell death was measured using a caspase activity assay. Again, a docking study was done to reinforce the findings from the primary in vitro experiment, though this time between baicalein and caspase-3 (binding affinity: -7.1 kcal/mol). Despite mixed observations in concentration dependence, caspase activity, relative to control, reached a maximal increase of 88.6% (p 0.01), and results from the MTT assay demonstrated a survival rate, relative to control, of as low as 59.64%. Considerations for future studies include the testing of baicalein in vivo and on more aberrative CRC cell lines.
