Genome profiling of mismatch repair genes in eight types of tumors

Cell Cycle. 2021 Jun;20(11):1091-1106. doi: 10.1080/15384101.2021.1922160. Epub 2021 May 9.

Abstract

Mismatch repair (MMR) plays an important role in the occurrence and development of tumors. At present, it is widely believed that MMR is a protective mechanism of tumors that plays a critical role in the progresses of cancer. In this study, 34 genes related to MMR selected from Gene Ontology (GO) database were scored by single sample Gene sets enrichment analysis (ssGSEA), and eight cancers were screened from 23 TCGA solid cancers to investigate the clinical significance of MMR score. MMR had different effects on the prognosis of the eight tumors, with a protective effect in three cancers and functioning as a risk factor in the remaining five cancers. We used unsupervised clustering to divide the patients into four clusters. We found that the immune and metabolic status of the four clusters were extremely different, among which cluster1 had the lowest tumor purity and the most complex microenvironment; this may explain its poor prognosis and immunotherapy effect. In summary, MMR scores can improve the predictive ability and provide effective guidance for immunotherapy in individual type of tumors.

Keywords: Pan cancer; immune microenvironment; mismatch repair.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics*
  • DNA Mismatch Repair / genetics*
  • Databases, Genetic
  • Genome / genetics*
  • Humans
  • Neoplasms / diagnosis
  • Neoplasms / genetics*
  • Sequence Analysis, RNA / methods*
  • Transcriptome / genetics*
  • Tumor Microenvironment / genetics

Substances

  • Biomarkers, Tumor

Grants and funding

This work was supported by National Natural Science Foundation of China (Grant No. 81872054 and 81902546).