The Novel Ferroptosis-related Gene Markers Predicting The Survival In Gastric Cancer Patients

Background: Gastric cancer(GC)is a common malignant tumor derived from gastric mucosa epithelium.Ferroptosis is an Fe-dependent novel programmed cell death mode different from apoptosis,cell necrosis and autophagy.Current studies have shown that ferroptosis plays an important role in cancer biology.Extracellular matrix(ECM)has been confirmed to play an important role in tumor cell proliferation,apoptosis,metabolism and differentiation,and as an important component of the tumor microenvironment,it interacts with the immune microenvironment and affects the occurrence and development of tumors.Objective: In this study,we constructed a prognostic model based on the ferroptosis-related genes associated with prognosis to better predict the prognosis of patients with GC.And the role of the ferroptosis-related genes in GC was preliminarily discussed.Methods: GC data were downloaded from the TCGA database.Furthermore,259ferroptosis-related genes were acquired with the Ferr Db database.COX regression analysis was used to screen ferroptosis-related genes related to GCs prognosis,and these genes constructed the prediction model.The risk score of the model and clinical data of GC were further analyzed to get the correlation between the model and the overall survival(OS)rate and clinicopathological features.Finally,GO and KEGG enrichment analysis was carried out on the genes of the model.To further analyze the correlation between the genes in the model and tumor immunity,ss GSEA was used to score immune cells and calculate immune-related pathways activity quantitatively.In the construction of prognosis model,SLC1A4 was screened out from the ferroptosis-related genes for further verification.The SLC1A4 protein expression level was detected by immunohistochemistry and mRNA expression level was detected by q RT-PCR from the tissue samples of patients with GC who had been resected.Finally,the correlation between SLC1A4 expression level and gastric cancer was analyzed.Results: We identified 11 genes associated with Ferroptosis(NOX4,NOX5,SLC1A5,GLS2,MYB,TGFBR1,NF2,ZFP36,DUSP1,SLC1A4,SP1),which affect the prognosis of patients with GC.The SLC1A4 expression in GC tissues was selected for verification,and the results showed that the expression of SLC1A4 in GC tissues was up-regulated and related to the poor prognosis of patients.Conclusion: In this study,a series of bioinformatics analyses were carried out on the ferroptosis-related genes with different prognosis in GC tissues and normal tissues,and11 ferroptosis-related genes were screened out that affected the prognosis of GC patients.Among them,SLC1A4 has been proved to be up-regulated in GC,which is expected to provide a new reference and research direction for gastric cancer screening,targeted therapy and prognosis evaluation.