ArticleOncology letters2020
Somatic mutations in genes associated with mismatch repair predict survival in patients with metastatic cancer receiving immune checkpoint inhibitors.
Article in Oncology letters, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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4 citing papers in PubMed, 5 citations in OpenAlex.
- Case report: Immunotherapy guided by molecular profiling of tumors: illustrative cases and literature review.Frontiers in medicine · 2024Article
- A rare case of sporadic mismatch repair deficient pancreatic ductal adenocarcinoma that responded to ipilimumab and nivolumab combination treatment: case report.Journal of gastrointestinal oncology · 2023Article
- Incidence, clinicopathologic, and genetic characteristics of mismatch repair gene-mutated glioblastomas.Journal of neuro-oncology · 2021Article
- Aberrant DNA repair as a potential contributor for the clonal evolution in subsets of anaplastic thyroid carcinomas arising through dedifferentiation: implications for future therapeutic algorithms?Cancer drug resistance (Alhambra, Calif.) · 2020Article
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Authors and funding
8 authors at 2 institutions in 1 country.
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Abstract
Immune checkpoint inhibitors (ICIs) have emerged as one of the most promising therapeutic options for patients with advanced cancer. The aim of the present study was to investigate the prognostic value of somatic mutations in mismatch repair (MMR) genes in metastatic cancers after ICI treatment, as well as their association with tumor mutational burden (TMB). Information regarding gene mutations in mismatch repair and the survival time of patients with advanced cancer following ICI treatment was collected from the cBioPortal database. The prognostic value of somatic mutations in MMR genes and the association between the mutation status and TMB score were analyzed among multiple types of cancer. Somatic mutation frequency in the MMR genes was identified to be 7% among all patients, which varied across different types of cancer. Somatic mutations in the MMR genes were associated with improved overall survival time in all tested patients (P=0.004). Following stratification by type of ICI treatment, a significant association was observed between somatic mutations in the MMR genes and overall survival time in patients treated with cytotoxic T-lymphocyte-associated protein 4 inhibitors (P=0.01). In addition, marked but non-significant association between somatic mutations in the MMR genes and overall survival time was revealed in patients administered with programmed death-1/programmed death-ligand-1 inhibitors (P=0.09). Multivariate Cox proportional hazards regression analysis demonstrated that somatic mutations in MMR genes were significantly associated with overall survival time (hazard ratio, 0.683; 95% confidence interval, 0.497-0.938; P=0.01). Patients with somatic mutations in the MMR genes demonstrated higher TMB compared with those not harboring mutations (P<0.01). The results of the present study suggested that somatic mutations in the MMR genes may be used as a prognostic marker of a positive outcome in patients with metastatic cancer receiving ICI treatment, since somatic mutations in the MMR genes may be one of the main factors affecting the tumor mutation load.
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