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Pan-cancer analysis of SETD2 mutation and its association with the efficacy of immunotherapy.

ABSTRACT: Histone methyltransferase SETD2 plays a critical role in maintaining genomic integrity and stability. Here, we investigated the characteristics of SETD2 somatic mutation in the cancer genome atlas pan-cancer cohort. Our data revealed that, compared with SETD2 nonmutant patients, SETD2 mutant patients had higher tumor mutation burden and microsatellite instability. In addition, the transcriptions of most genes related to immune activities were upregulated in patients with SETD2 mutant tumors. Further examination of cancer patients treated with immune checkpoint inhibitors suggested SETD2 mutation was associated with favorable clinical outcomes. These results have implication for the personalization of cancer immunotherapy.

SUBMITTER: Lu M

PROVIDER: S-EPMC8203790 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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Pan-cancer analysis of SETD2 mutation and its association with the efficacy of immunotherapy.

Lu Mingdong M Zhao Bin B Liu Mengshan M Wu Le L Li Yingying Y Zhai Yingna Y Shen Xian X

NPJ precision oncology 20210614 1

Histone methyltransferase SETD2 plays a critical role in maintaining genomic integrity and stability. Here, we investigated the characteristics of SETD2 somatic mutation in the cancer genome atlas pan-cancer cohort. Our data revealed that, compared with SETD2 nonmutant patients, SETD2 mutant patients had higher tumor mutation burden and microsatellite instability. In addition, the transcriptions of most genes related to immune activities were upregulated in patients with SETD2 mutant tumors. Fur ...[more]

PMID: 34127768

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Project description:Background: The clinical implementation of immune-checkpoint inhibitors (ICIs) targeting CTLA4, PD-1, and PD-L1 has revolutionized the treatment of cancer. However, the majority of patients do not derive clinical benefit. Further development is needed to optimize the approach of ICI therapy. Immunotherapy combined with other forms of treatment is a rising strategy for boosting antitumor responses. CD93 was found to sensitize tumors to immune-checkpoint blocker therapy after the blockade of its pathway. However, its role in immune and ICB therapy across pan-cancer has remained unexplored. Methods: In this study, we provide a comprehensive investigation of CD93 expression in a pan-cancer manner involving 33 cancer types. We evaluated the association of CD93 expression with prognosis, mismatch repair, tumor mutation burden, and microsatellite instability, immune checkpoints, tumor microenvironment, and immune using multiple online datasets, including The Cancer Genome Atlas, Cancer Cell Line Encyclopedia, Genotype Tissue-Expression, cBioPortal, Tumor Immune Estimation Resource database, and Tumor Immune Single-cell Hub. Results: CD93 expression varied strongly among cancer types, and increased CD93 gene expression was associated with poor prognosis as well as higher immune factors in most cancer types. Additionally, the level of CD93 was significantly correlated with MMR, TMB, MSI, immune checkpoints, TME, and immune cell infiltration. Noticeably, our results mediated a strong positive contact between CD93 and CAFs, endothelial cells, myeloid dendritic cells, hematopoietic stem cells, mononuclear/macrophage subsets, and neutrophils while a negative correlation with Th1, MDSC, NK, and T-cell follicular helper in almost all cancers. Function analysis on CD93 revealed a link between itself and promoting cancers, inflammation, and angiogenesis. Conclusion: CD93 can function as a prognostic marker in various malignant tumors and is integral in TME and immune infiltration. Inhibition of the CD93 pathway may be a novel and promising strategy for immunotherapy in human cancer. Further explorations of the mechanisms of CD93 in the immune system may help improve cancer therapy methods.

Dataset Information

Pan-cancer analysis of SETD2 mutation and its association with the efficacy of immunotherapy.

Publications

Pan-cancer analysis of SETD2 mutation and its association with the efficacy of immunotherapy.

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