Research Paper Volume 13, Issue 6 pp 9043—9055
Mucin 4 mutation is associated with tumor mutation burden and promotes antitumor immunity in colon cancer patients
- 1 Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
- 2 Department of Clinical Nutrition, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
- 3 Department of Hepatobiliary Surgery, The Affiliated Hospital of North Sichuan Medical College, Sichuan 637000, China
- 4 Department of Oncology, The Cancer Center of the Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai 519000, China
- 5 Department of Gastrointestinal Surgery, The Affiliated Hospital of North Sichuan Medical College, Sichuan 637000, China
Received: October 15, 2020 Accepted: February 27, 2021 Published: March 14, 2021https://doi.org/10.18632/aging.202756
How to Cite
Copyright: © 2021 Peng 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.
At present, immunotherapy is widely used for different mismatch repair (dMMR) or highly microsatellite instability (MSI-H) colorectal cancer patients, and tumor mutation burden (TMB) is a valuable independent predictor of response to immunotherapy. However, specific gene mutations and their relationship with TMB and tumor-infiltrating immune cells in colon cancer remains unclear. In the present study, we analyzed somatic mutation data of colon cancer from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) datasets, and found that 17 frequently mutated genes were occurred in both cohorts, including APC, TP53, TNN, KRAS, MUC16, MUC4 (mucin 4), SYNE1, FLG, FAT4, OBSCN, FAT3, RYR2, PIK3CA, FBXW7, DNAH11, MUC5B and ZFHX4. Interestingly, only MUC4 mutation was associated with higher TMB and patient clinical prognosis among the 17 mutated genes. Moreover, according to gene set enrichment analysis (GSEA) and the CIBERSORT algorithm, we revealed that MUC4 mutation activated signaling pathways involved in the immune system and enhanced the antitumor immune response. In conclusion, MUC4 may have important clinical implications for immune therapy of colon cancer.
CTLs: cytotoxic T lymphocytes; dMMR: different mismatch repair; GSEA: Gene set enrichment analysis; ICGC: International Cancer Genome Consortium; ICPI: immune checkpoint inhibitor; mCRC: metastatic colorectal cancer; MSI-H: Highly microsatellite instability; MUC4: mucin 4; NES: normalized enrichment score; PD-L1: programmed death ligand 1; PFS: progress-free survival; RFS: relapse free survival; TCGA: The Cancer Genome Atlas; TMB: Tumor mutant burden; Tregs: regulatory T cells.