Abstract
Background T cell-mediated antitumor immune response is the basis of colorectal cancer (CRC) immunotherapy. Cholesterol plays an important role in T cell signal transduction and function. Apolipoprotein E (APOE) plays a major role in cholesterol metabolism. Objective To screen and analyze key markers involved in the anticolon cancer response of CD8+ T cells through the regulation of cholesterol metabolism. Methods Based on the median cutoff of the expression value of APOE according to the data downloaded from The Cancer Genome Atlas and Gene Expression Omnibus database, patients were grouped into low and high expression groups. Differences in clinical factors were assessed, and survival analysis was performed. Differentially expressed genes (DEGs) in the high and low expression groups were screened, followed by the analysis of differences in tumor-infiltrating immune cells and weighted gene coexpression network analysis results. The closely related genes to APOE were identified, followed by enrichment analysis, protein–protein interaction (PPI) network analysis, and differential expression analysis. Immunohistochemical staining (IHC) was used to detect the expression of CD8 in CRC tissues. Results There were significant differences in prognosis and pathologic_N between the APOE low and high expression groups. A total of 2,349 DEGs between the high and low expression groups were selected. A total of 967 genes were obtained from the blue and brown modules. The probability of distribution of CD8+ T cells differed significantly between the two groups, and 320 closely related DEGs of APOE were screened. Genes including the HLA gene family, B2M, IRF4, and STAT5A had a higher degree in the PPI network. GEO datasets verified the prognosis and the related DEGs of APOE. IHC staining verified the relationship between the distribution of CD8+ T cells and APOE expression. Conclusion Genes including the HLA gene family, B2M, IRF4, and STAT5A might be the key genes involved in the anticolon cancer response of CD8+ T cells through the regulation of cholesterol metabolism.
Highlights
Colon cancer is a major health problem worldwide because it is the second leading cause of cancer-related deaths [1]
To ensure the reliability of the screening results of key network modules, the disease-related key network modules were analyzed again by calculating the absolute value of gene significance (GS) within the module, and the results showed that the blue and brown modules had a higher GS
Genes including the histocompatibility leukocyte antigen (HLA) gene family, B2M, and interferon regulatory factor 4 (IRF4) had a higher degree in the protein–protein interaction (PPI) network, and STAT5A was regulated by numerous miRNAs in the ceRNA network
Summary
Colon cancer is a major health problem worldwide because it is the second leading cause of cancer-related deaths [1]. A high-fat diet is widely involved in various pathological conditions, such as obesity and metabolic diseases, which may promote the development of colon cancer [8]. To screen and analyze key markers involved in the anticolon cancer response of CD8+ T cells through the regulation of cholesterol metabolism. Expressed genes (DEGs) in the high and low expression groups were screened, followed by the analysis of differences in tumor-infiltrating immune cells and weighted gene coexpression network analysis results. E probability of distribution of CD8+ T cells differed significantly between the two groups, and 320 closely related DEGs of APOE were screened. Genes including the HLA gene family, B2M, IRF4, and STAT5A might be the key genes involved in the anticolon cancer response of CD8+ T cells through the regulation of cholesterol metabolism
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