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Updated: Nov 28, 2025
Deficient Pms2, ERCC1, Ku86, CcOI in Field Defects During Progression to Colon Cancer
Published on: July 28, 2010
KRAS mutations are negatively correlated with immunity in colon cancer
Xiaorui Fu1,2, Xinyi Wang1,2, Jinzhong Duanmu1
1Department of Gastrointestinal Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People's Republic of China.
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.
Insights
KRAS mutations are common in colon cancer and impact patient prognosis. These mutations are linked to reduced immune cell activity within tumors, suggesting new therapeutic strategies.
Area of Science:
- Oncology
- Genomics
- Immunology
Background:
- Colon cancer exhibits significant heterogeneity, necessitating exploration of specific molecular targets.
- Understanding gene mutations is crucial for developing effective colon cancer therapeutics.
Purpose of the Study:
- To investigate the landscape of somatic mutations in colon cancer.
- To evaluate the prognostic and predictive value of KRAS mutations.
- To explore the relationship between KRAS mutations and the tumor immune microenvironment.
Main Methods:
- Analysis of colon cancer samples from The Cancer Genome Atlas and the International Cancer Genome Consortium.
- Utilized ESTIMATE analysis to assess tumor purity, immune, and stromal scores.
- Employed Gene Set Enrichment Analysis (GSEA) to evaluate immune-related gene expression and activity.
Main Results:
- KRAS mutations, specifically rs121913529, were frequent and demonstrated prognostic value.
- The KRAS-mutated group showed higher tumor purity and lower immune/stromal scores.
- KRAS mutations correlated with decreased tumor-infiltrating lymphocytes, inflammation, and cytolytic activity, alongside lower HLA and checkpoint gene expression.
Conclusions:
- KRAS mutations have significant prognostic and predictive implications in colon cancer.
- KRAS mutations are associated with an altered immune microenvironment, characterized by reduced immune infiltration and activity.
- Identification of 24 differentially expressed immune-related genes offers insights into KRAS-mediated immune alterations.
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