Research Paper Volume 13, Issue 1 pp 750—768
KRAS mutations are negatively correlated with immunity in colon cancer
- 1 Department of Gastrointestinal Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People's Republic of China
- 2 Queen Mary College, Medical Department, Nanchang University, Nanchang, Jiangxi, People's Republic of China
Received: March 27, 2020 Accepted: October 8, 2020 Published: November 26, 2020
https://doi.org/10.18632/aging.202182How to Cite
Copyright: © 2020 Fu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
The heterogeneity of colon cancer tumors suggests that therapeutics targeting specific molecules may be effective in only a few patients. It is therefore necessary to explore gene mutations in colon cancer. In this study, we obtained colon cancer samples from The Cancer Genome Atlas, and the International Cancer Genome Consortium. We evaluated the landscape of somatic mutations in colon cancer and found that KRAS mutations, particularly rs121913529, were frequent and had prognostic value. Using ESTIMATE analysis, we observed that the KRAS-mutated group had higher tumor purity, lower immune score, and lower stromal score than the wild-type group. Through single-sample Gene Set Enrichment Analysis and Gene Set Enrichment Analysis, we found that KRAS mutations negatively correlated with enrichment levels of tumor infiltrating lymphocytes, inflammation, and cytolytic activities. HLA gene expression and checkpoint-related genes were also lower in the KRAS-mutated group. Finally, we found 24 immune-related genes that differed in expression between the KRAS-mutated and wild-type samples, which may provide clues to the mechanism of KRAS-related immune alteration. Our findings are indicative of the prognostic and predictive value of KRAS and illustrate the relationship between KRAS mutations and immune activity in colon cancer.
Abbreviations
The Cancer Genome Atlas: TCGA; International Cancer Genome Consortium: ICGC; Single-Sample Gene Set Enrichment Analysis: ssGSEA; Gene set enrichment analysis: GSEA; microsatellite instability: MSI; tumor-necrosis factor: TNF; transforming growth factor-β: TGF-β; human leukocyte antigen: HLA; programmed death-1 receptor: PD-L1; microsatellite stable: MSS; tumor mutational burden: TMB; natural killer cell: NK cell; tumor infiltration lymphocyte: TIL; granzyme A: GZMA; perforin 1: PRF1; Mutation Annotation Format: MAF.