Bioinformatics Study Of C3AR1 As A Prognostic Marker For Gastric Cancer

According to the national centers for disease control and prevention on the newly published in the Lancet about China’s population disease morbidity and mortality related research shows that gastric cancer ranks third in all tumors in most patients with gastric cancer was confirmed in phase progress or distant metastasis,gastric cancer treatments currently limited to endoscopic therapy,surgery and radiation and chemotherapy.Immune checkpoint therapy has become a hot spot in tumor immunotherapy in recent years.It has achieved remarkable results in the treatment of melanoma,non-small cell lung cancer,prostate cancer and other cancers.However,in the treatment of gastric cancer,the monoclonal antibody against PD-1 has been excluded.There are no other immunotherapies approved for the treatment of gastric cancer in the world except for the approval of the market in my country.Therefore,to explore new more effective gastric cancer immunotherapy targets appears imminent Studies have pointed out that the expression level of the immune checkpoints and tumor infiltration of immune cells such as macrophages,neutrophils abundance affects the prognosis and therapeutic effect of immune therapy,and some of the biomarkers of tumor patients and the expression of immune checkpoints and tumor immune cell infiltration.Therefore,in this study,a possible prognostic marker for gastric cancer was discovered by using bioinformatics methods,and verified by online bioinformatics tools and software,as well as a preliminary analysis of the influence of this marker on the prognosis of gastric cancer.Objective:The aim of this study was to find the prognostic biomarker genes of gastric cancer and study the correlation between them and gastric cancer immune cell infiltration,so as to provide new potential targets and feasible research ideas for the immunotherapy of gastric adenocarcinoma.Methods:(1)Screening possible prognostic marker genes for gastric adenocarcinoma:Data mining through multiple online bioinformatics analysis platforms found the gene sets related to PDL2,TIM-3,and VSIG4 in gastric adenocarcinoma(STAD),and integrated the gene sets analyzed by each platform Take the intersection and get the target gene set.Then put the genes in the gene set to multiple online bioinformatics analysis platforms for differential expression analysis and prognosis analysis,and screen out the gene C3AR1,which has different expression and affects the prognosis,as the target gene.And carry out correlation analysis with the found gastric adenocarcinoma markers.(2)To explore the possible biological functions of the target gene:GSEA software was used for GO analysis and KEGG analysis to explore the possible biological functions of the target gene C3AR1 in the occurrence and development of gastric cancer.(3)To explore the influence of target gene on the degree of immune cell infiltration:The correlation between the infiltration of various immune cells(B cells,CD4+T cells,CD8+T cells,macrophages,neutrophils,and dendritic cells(DCs))and the expression level of C3AR1 in gastric cancer was analyzed by using the online bioinformatics analysis platform Timer.(4)The correlation between the target gene and the immune cell marker set was further analyzed:The gene marker sets of various immune cells were further summarized,and the correlation between the target gene and C3AR1 was analyzed through GEPIA and TIMER online bioinformatics analysis platform.Results:(1)The results of the online bioinformatics analysis platform were screened,and it was found that the expression of C3AR1 was significantly different in gastric cancer.It was highly expressed in gastric cancer,and the prognosis of patients with high expression of C3AR1 was worse than that of patients with low expression of C3AR1.Moreover,the correlation analysis showed that C3AR1 had a high correlation with STAD tissue markers.(2)Through the analysis of GSEA software,C3AR1 is involved in a variety of immune-related biological processes and pathways in STAD,and it can be speculated that C3AR1 affects the tumor immune process in STAD.(3)By exploring the relationship between the expression of C3AR1 and the infiltration of gastric cancer immune cells and the correlation analysis of C3AR1 and the gene marker set of immune cells,it was found that the expression of C3AR1 was strongly positively correlated with the infiltration of mononuclear tumor-associated macrophages M2 macrophage dendritic cell failure T cells.Conclusions:(1)High expression of C3AR1 was positively associated with poor prognosis and increased tumor immunoinvasion.(2)C3AR1 can be used as a marker of prognosis and immune infiltration in the pathogenesis of STAD.(3)C3AR1 can promote M2 macrophage polarization and T cell failure,leading to immune escape of STAD.