Exploring The Genes That Affect The Prognosis Of Colon Cancer And Their Correlation With Immune Infiltrating Cells

Objective: As the most important component of tumor microenvironment,tumor-associated immune infiltrating cells play an important role in regulating tumor growth.Based on bioinformatics,we screen immune-related differentially expressed genes affecting the prognosis of colon cancer and analyze the correlation with immune infiltration cell,so as to provide theoretical guidance for exploring the occurrence and development of tumor,evaluating the prognosis of patients,and developing new immunotherapy strategies.Methods: RNA-seq expression data of colon cancer and corresponding clinical data were downloaded from TCGA database to screen out the differentially expressed genes between colon cancer tumor tissues and normal colon tissues.IMMPORT,IRIS,and Innate DB databases were searched to download the immune-related genes for Venn intersection with differentially expressed genes,and immune-related differentially expressed genes were obtained..Based on the gene set,GO and KEGG enrichment analysis was performed and single-gene COX regression analysis was used to screen out differentially expressed genes affecting prognosis.The proteinprotein interaction network was constructed and the core genes were screened according to the number of adjacent nodes.The target genes for downstream research were obtained by intersecting with the differentially expressed genes that affect prognosis.Then,the expression of target genes in pan-carcinoma was analyzed by using TIMER online database.GEO database and real-time quantitative PCR were used to verify the expression difference of target genes in colon cancer tissues and cells.Kaplan-Meier survival curve was drawn and clinical correlation analysis was performed.GSEA enrichment analysis was performed for the target gene involving in the biological process.CIBERSORT algorithm was used to analyze the relationship between target gene expression and immune infiltrating cells.Results: In this study,2642 differentially expressed genes were screened from the TCGA database,and 760 differentially expressed immune-related genes were obtained after intersection with immune-related genes.The immunorelated differentially expressed gene PPARGC1 A,which affects the prognosis of colon cancer,was screened by COX regression analysis of protein interaction network and single gene.The expression level of PPARGC1 A was significantly down-regulated in urothelial carcinoma of bladder,invasive carcinoma of breast,colon carcinoma,esophageal carcinoma,multiforming glioblastoma,head and neck carcinoma,clear cell carcinoma of kidney,papillary cell carcinoma of kidney,hepatoma of lung,adenocarcinoma of lung,squamous cell carcinoma of lung,and significantly up-regulated in chromophobic cell carcinoma of kidney.PPARGC1 A expression was confirmed to be significantly down-regulated in colon cancer tumor paired and unpaired tissue samples,as well as in colon cancer cell HCT116.The expression level of PPARGC1 A was significantly correlated with the survival time of patients,that is,when the expression level of PPARGC1 A was high,the survival time of colon cancer patients was longer.In clinical correlation analysis,the expression of PPARGC1 A was significantly down-regulated in stage IV patients compared with stage II patients;PPARGC1A expression was significantly down-regulated in stage M1 patients compared with stage M0 patients.GSEA single gene enrichment analysis showed that PPARGC1 A plays an important role in the positive regulation of β-like protein formation and amyloid precursor catabolism,and is involved in ribosome,RNA polymerase,cytoplasmic DNA receptor and other signaling pathways.Finally,CIBERSORT algorithm was used to analyze the expression of PPARGC1 A,which was positively correlated with the number of dendritic cells,static CD4+ T cells and gamδ T cells,but negatively correlated with NK cells,M0 macrophages,M2 macrophages and neutrophils.Conclusion: PPARGC1 A,as an immune-related differentially expressed gene affecting the prognosis of colon cancer,is lower expression in colon cancer tumor tissues,affecting the distant metastasis of tumors.The PPARGC1 A expression was significantly correlated with the survival time of patients,that is,patients with low expression of PPARGC1 A had shorter survival time.It may be related to the increase of CD4+T cells and dendritic cells content,and the decrease of NK cells,M0 macrophages,M2 macrophages and neutrophils in colon cancer tumor tissues.