Exploring Prognosis,Tumor Microenvironment And Tumor Immune Infiltration In Gastric Cancer Based On Complement Family Gene-related Models

BACKGROUND: The complement system is integral to the innate and adaptive immune response,helping antibodies eliminate pathogens.complement system is associated with various inflammatory processes,the pathogenesis of immune diseases,and tumor growth.However,its role in the tumor microenvironment(TME)of gastric cancer(GC)remains unclear.METHODS: Using data from The Cancer Genome Atlas(TCGA),this research evaluated the expression,copy number variations,and frequency of somatic mutations of complement family genes in GC.A prognostic model based on the complement genes family was developed via Lasso and Cox regression analyses,with the TCGA cohort serving as the training dataset and the International Gene Expression Omnibus(GEO)cohort serving as the validation set.Kaplan-Meier and receiver operating characteristic analyses verified the accuracy of the prognostic model.Furthermore,the association among the prognostic model,immune checkpoints,and immune cells was examined.The expression of C5 a receptor 1(C5a R1)in GC and normal gastric mucosa tissues was compared using data retrieved from the Gene Expression Omnibus(GEO)and Cancer Genome Atlas(TCGA)databases,and the results were validated via in vitro q RT-PCR and immunohistochemical analyses.The relationship between C5 a R1expression and the overall survival(OS)of patients with GC was analyzed using the Kaplan–Meier method.Subsequently,enrichment analysis was performed,and signaling pathways were screened.C5 a R1 expression was also correlated with genes related to the immune checkpoint and immune cell infiltration.RESULTS: The results revealed that high-risk patients exhibited an unfavorable outcome as opposed to those in the low-risk category.The prognostic model-derived risk score was shown to serve as a prognostic marker of GC in an independent way,as per the multivariate Cox analysis.The core gene C5 a R1 expression was enhanced in GC tissues when compared to normal gastric tissues,and patients with high expression of C5 a R1 had a worse 10-year OS compared to those showing low expression of C5 a R1.Functional analysis revealed that C5 a R1 is a gene related to the immune that may play a crucial role in inflammatory and tumor immune responses.Additionally,C5 a R1 showed a positive correlation with most immune checkpoint-related genes and a negative correlation with natural killer(NK)cells,dendritic cells(DCs),and CD8+ T cells.Immune evasion risk was observed to be significantly greater in patients with higher expression of C5 a R1 than in those with lower expression.CONCLUSION: The results of this study show that the prognostic model constructed by complement genes can well predict the prognosis of gastric cancer,and that C5 a R1 in complement genes shapes a non-inflammatory tumor microenvironment in gastric cancer and is associated with immune escape.