Correlation analysis of pyroptosis-related genes with prognosis and im-mune infiltration in gastric cancer
Objective To screen prognostic pyroptosis-related genes(PRGs)in gastric cancer through bioinformatics,construct and evaluate risk models,analyze the correlation between PRGs and immune infiltration,and validate new targets for gastric cancer treatment.Methods The transcriptome and clinical data of gastric cancer were obtained from the cancer genome atlas(TCGA)database,and differentially expressed PRGs were screened.Univariate Cox regression and LASSO regression were used to analyze differentially expressed PRGs and construct a prognostic model.Kaplan-Meier survival curve and receiver operator characteristic curve were used to evaluate the accuracy and prognostic value of the model.Patients were divided into the high-risk group and the low-risk group based on the median risk score,and the correlation between risk score and prognosis was evaluated by using Cox regression risk model.The gastric cancer gene chip dataset GSE84437 was used as an external validation for prediction models.The mRNA and protein expression levels of SERPINE1,Caspase-1,and NLRP3 were detected by using RT-qPCR and Western blott.Results A total of 35 differentially expressed PRGs were screened,among which five PRGs(CRTAC1,GPX3,IRGM,RGS2,and SERPINE1)were included in the risk model construction.Age,M-stage,N-stage,and risk score were independent influencing factors for survival in patients in TCGA cohort(P＜0.05);age,T-stage,and N-stage were independent influencing factors for survival in patients in gene expression omnibus(GEO)cohort(P＜0.05).The immune cell infiltration level and immune related pathway generally activity of the high-risk group in TCGA and GEO cohorts were higher than those of the low-risk group(P＜0.05).CRTAC1 was positively correlated with the infiltration levels of CD4+T cells(r=0.488),macrophages(r=0.588),and dendritic cells(r=0.332)(P＜0.01);GPX3 was positively correlated with the infiltration levels of CD4+T cells(r=0.372),macrophages(r=0.572),and dendritic cells(r=0.406)(P＜0.01);RGS2 was positively correlated with the infiltration levels of CD4+T cells(r=0.343),macrophages(r=0.526),and dendritic cells(r=0.326)(P＜0.01);IRGM(r=0.327)and SERPINE1(r=0.310)were positively correlated with the infiltration level of macrophages(P＜0.01).The expression level of SERPINE1 in gastric cancer tissue was higher than that in normal gastric tissue(P＜0.05);the survival time of the high expression SERPINE1 group was shorter than that of the low expression SERPINE1 group(P＜0.01).The mRNA and protein expression levels of SERPINE1,Caspase-1,and NLRP3 in the interference group were lower than those in the negative control group(P＜0.05).Conclusion Screening five PRGs by using bioinformatics methods to construct a gastric cancer prognosis model.High expression of SERPINE1 is associated with poor prognosis of gastric cancer and may be involved in regulating the NLRP3/Caspase-1 cell pyroptosis pathway.
Gastric cancerPyroptosis-related genesThe cancer genome atlas databasePrognosis risk modelImmune infiltration
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