Development And Evaluation Of A Prognostic Model For Gastric Cancer By Screening Apoptosis-related Genes Related To Prognosis Of Gastric Cancer

Background and ObjectivesAs the prognosis of gastric cancer(GC)patients is poor and heterogeneous,effective therapeutic targets and more accurate prognostic assessment methods are urgently needed.In recent years,it has been found that abnormalities of apoptosis and apoptosis-related genes(ARGs)are closely related to the occurrence,development and metastasis of GC.Therefore,correcting these abnormalities to treat GC may be a promising treatment method.In this study,the prognostic model of GC patients was established based on the screening of ARGs related to prognosis of GC patients,and the prognostic value of the prognostic model was evaluated and verified in order to achieve accurate diagnosis and treatment of GC patients and improve their prognosis.MethodsFirstly,sequencing and clinical information of GC samples and normal samples were extracted from The Cancer Genome Atlas(TCGA)database,and ARGs differentially expressed between The two samples were screened.Secondly,Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Gnomes(KEGG)enrichment analysis were used to identify the signaling pathways and biological processes involved in differential Genes.Meanwhile,protein-protein interaction network(PPI)was constructed to understand the interaction between differentially expressed proteins.Univariate Cox regression analysis and multivariate Cox regression analysis based on Akaike Information Criterion(AIC)were used to screen the key genes for prognosis of GC patients.By combining the expression level and risk coefficient of key genes,this study constructed a prognostic risk score for GC patients.Receiver Operating characteristic(ROC)curve,Kaplan-Meier survival curve and external queues from Gene Expression Omnibus(GEO)databases were used to evaluate the predictive effectiveness of risk scoring models.ResultsIn this study,38 differentially expressed ARGs in GC and normal tissues were screened out.The results of enrichment analysis showed that most of the genes were involved in the regulation of cell cycle,external signaling pathways of apoptosis,p53 signaling pathway and PI3K-Akt signaling pathway.Among them,10 differential genes(CAV1,DCN,F2,F2R,GADD45B,GPX3,IGFBP6,LUM,PDGFRB)were associated with the prognosis of GASTRIC cancer,and 3 differential genes(CAV1,F2,LUM)were identified as key genes for the prognosis of GC patients.In addition,the risk score constructed in this study was proved to have good predictive efficacy(AUC=0.631),and the results of multivariate Cox regression analysis showed that risk score was an independent risk factor for prognosis of GC patients.By integrating the results of multivariate Cox regression analysis,this study constructed a prognostic model that can be used in clinical practice.The calibration curve and C index(C index=0.607)confirmed the accuracy of the prognostic model,ConclusionsThe ARGs screened in this study can realize the early diagnosis of gastric cancer patients and provide a new target for molecular therapy of GC.In addition,the prognostic model based on ARGs can be used as a supplement to the existing GC staging system,which can help clinicians to make more accurate diagnosis and treatment decisions for GC patients by risk stratification.