Multi-omics Analysis Identifying CD58 Plays Important Role on Prognosis of Colorectal Cancer

Abstract

AbstractThe immunotherapy is a programming therapy of cancer, so new immunotherapy target genes would be urgently demanded at present. Although The Cancer Genome Atlas Program (TCGA) provided more than 11,000 patients’ multi-omics data of more than 33 cancers, the heterogeneity of tumor tissue may still mask the immune-associated gene differential expression. In our study, to address the heterogeneity masked by the bulk RNA-Seq, TCGA data were first dividend into 26 types cancers by their high immune infiltration and low immune infiltration through single-sample gene set variation analysis to detect immune-associated gene, and single-cell RNA-Seq were than reanalyzed to prove the result we received in RNA-Seq. In order to verify our result in cell lines, a series of experiments were performed on two different microsatellite state cell lines: HCT116 (microsatellite instability high) and HT29 (microsatellite stability) because of colorectal cancer had its corresponding cell lines. Our results suggested that high expression levels of CD58, an immune-related gene, was masked by the bulk RNA-Seq and had a significant effect on the prognosis of patients with microsatellite instability high. The high expression of CD58 inhibited the proliferation and invasion of cancer cells in HCT116, which had highly unstable microsatellites, but had no effect on HT29, which had stable microsatellites. The high CD58 expression combined with microsatellite instability high statuses were the important molecular targets in the selection of immunotherapy methods in colorectal cancer. In short, our study provides new insight into detecting immune-associated gene in different cancer bulk RNA-Seq.