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

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

Chen Lijin
Li Yingying
Zhao Hong
Huang Jinyuan
Yan Huimeng
Lin Xiaoyan
Zhao Bin
Genes & Diseases第12卷, 第4期纸质出版 2025-07-01在线发表 2024-11-08
7800

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.

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BiomarkerCancerImmune checkpoint inhibitorImmunotherapyMesenchymal-epithelial transition factorTumor immunogenicity