MET Overexpression Is Associated with Superior Immunotherapy Benefit in Advanced Non-Small Cell Lung Cancer

作者：Hui Li, Lingzhi Hong, Pedro Rocha, Rafael Bach, Luisa M. Solis Soto, Waree Rinsurongkawong, Bingnan Zhang, Haniel A. Araújo, Yasir Y. Elamin, Mehmet Altan, Claudio A. Arrechedera, Jianling Zhou, Khaja Khan, Wei Lü, Elliana Young, Carl M. Gay, Tina Cascone, Lauren A. Byers, Ferdinandos Skoulidis, George R. Blumenschein, Frank V. Fossella, Anne S. Tsao, Marcelo V. Negrão, Natalie I. Vokes, Jia Wu, Hai T. Tran, Ignacio I. Wistuba, J. Jack Lee, Don L. Gibbons, Ara A. Vaporciyan, John V. Heymach, Xiuning Le, Jianjun Zhang · 发表于：Cancers · 年份：2025 · DOI：10.3390/cancers17233801 · 研究领域：Liver physiology and pathology、Lung Cancer Treatments and Mutations、Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis

Background/Objectives: MET overexpression is common in non-small cell lung cancer (NSCLC). The correlation between MET overexpression and immune checkpoint inhibitor (ICI) efficacy in NSCLC is underexplored. Methods: In this retrospective observational cohort study, we curated a dataset of 279 stage IV NSCLC patients who received ICI treatment and had MET expression assessed by CLIA-certified immunohistochemistry (IHC) assay. MET expression was graded on a scale from 0 to 3+, with overexpression defined as 2+ or 3+. Clinicopathological features associated with MET expression were assessed using logistic regression. Overall survival (OS) and progression-free survival (PFS) were evaluated via Kaplan–Meier analysis and the multivariate Cox proportional hazards model. To derive the most parsimonious and statistically robust models, stepwise refinement based on the Akaike Information Criterion (AIC) was applied. Results: MET overexpression was observed in 220 of 279 patients (78.9%). Adenocarcinoma histology (p = 0.003) and PD-L1 expression (p < 0.001) were independently associated with MET overexpression. Kaplan–Meier analysis showed patients with MET overexpression had significantly superior OS (p = 0.012) and PFS (p = 0.033). Full Cox regression analysis revealed that MET overexpression was associated with longer OS (p = 0.040), independent of PD-L1 levels. Patients with MET overexpression had numerically longer PFS (p = 0.145). Following adjustment for metastatic burden, th...