Pan-cancer analysis of MET mutation and its association with the efficacy of immune checkpoint blockade

Pan-cancer analysis of MET mutation and its association with the efficacy of immune checkpoint blockade

The mesenchymal-epithelial transition factor (MET) proto-oncogene plays important roles during tumor development. Recently, evidence has revealed MET signaling may impact tumor immunogenicity and regulate the immune response. Here we conducted a comprehensive bioinformatic and clinical analysis to e...

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Bibliographic Details
Main Authors: Lijin Chen, Yingying Li, Hong Zhao, Jinyuan Huang, Huimeng Yan, Xiaoyan Lin, Bin Zhao
Format: Article
Language:English
Published: KeAi Communications Co., Ltd. 2025-07-01
Series:Genes and Diseases
Subjects:
Biomarker
Cancer
Immune checkpoint inhibitor
Immunotherapy
Mesenchymal-epithelial transition factor
Tumor immunogenicity
Online Access:http://www.sciencedirect.com/science/article/pii/S2352304224002472
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Summary:The mesenchymal-epithelial transition factor (MET) proto-oncogene plays important roles during tumor development. Recently, evidence has revealed MET signaling may impact tumor immunogenicity and regulate the immune response. Here we conducted a comprehensive bioinformatic and clinical analysis to explore the characteristics of MET mutation and its association with the outcomes in pan-cancer immunotherapy. In 4149 patients with 12 tumor types treated with immune checkpoint inhibitors, MET mutation indicated favorable overall survival (hazard ratio = 0.61; 95% CI, 0.50–0.74; P < 0.001), progression-free survival (hazard ratio = 0.74; 95% CI, 0.60–0.92; P = 0.01), and objective response rate (40.3% vs. 28.1%; P = 0.003). Moreover, we developed a nomogram to estimate the 12-month and 24-month survival probabilities after the initiation of immunotherapy. Further multi-omics analysis on both intrinsic and extrinsic immune landscapes revealed that MET mutation enhanced tumor immunogenicity, enriched infiltration of immune cells, and improved immune responses. In summary, MET mutation improves cancer immunity and is an independent biomarker for favorable outcomes in pan-cancer immunotherapy. These results may influence clinical practices, guide treatment decision-making, and develop immunotherapy for personalized care.
ISSN:2352-3042

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