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- W3140035148 abstract "Background: Immunotherapies have dramatically improved survival of melanoma patients. MUC16 encodes cancer antigen 125 (CA125), which is frequently mutated in melanoma. However, association of MUC16 mutation with tumor mutation load (TML), microenvironment, outcome and immunotherapeutic efficacy in melanoma remains elusive.Methods: We obtained 467 melanoma samples from the Cancer Genome Atlas (TCGA). We correlated MUC16 mutation status with TML, multiple immune-related signals in microenvironment, dysregulated pathways and outcome. An independent dataset containing 183 samples was used for validation. The association of MUC16 mutation with immune checkpoint inhibitor (ICI) efficacy was estimated with 144 ICI treated patients from a published study.Findings: MUC16 mutation exhibited the most significant correlation with TML in TCGA cohort. In both cohorts, patients with MUC16 mutations had significantly higher TML than those without MUC16 mutations. Enriched pro-inflammatory CD8 T cells and M1 macrophages, abundant total immune cells infiltration, enhanced interferon gamma (IFNγ) and T cell-inflamed signatures, and increased cytolytic activity were associated with MUC16 mutation. Immune-suppressive M2 macrophages was enriched in MUC16 wild-type patients. Immune checkpoints expression were also elevated in patients with MUC16 mutation. Patients with MUC16 mutations exhibited significantly better prognosis in both cohorts. For patients received ICI treatment, MUC16 mutation was associated with better response rate and survival outcome in male group but not in female and overall group.Interpretation: MUC16 mutation was associated with high TML, immune-activated microenvironment and favorable prognosis in melanoma. Male patients with MUC16 mutations had better ICI therapy efficacy. These findings provide new implications for tailoring immunotherapeutic strategies of melanoma patients.Funding Statement: This study was supported by the Program for Changjiang Scholars and Innovative Research Team in University in China [IRT_14R40 to K. C.], and the National Natural Science Foundation of China [no. 31801117 to X. L.].Declaration of Interests: The authors stated: None.Ethics Approval Statement: This study has been approved by the Tianjin Medical University Cancer Institute and Hospital." @default.
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- W3140035148 date "2020-01-01" @default.
- W3140035148 modified "2023-10-16" @default.
- W3140035148 title "High Mutation Load, Immune-Activated Microenvironment, Favorable Outcome and Better Immunotherapeutic Efficacy of Patients with Melanoma Harboring <i>MUC16</i>/CA125 Mutation" @default.
- W3140035148 doi "https://doi.org/10.2139/ssrn.3520038" @default.
- W3140035148 hasPublicationYear "2020" @default.
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