{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T12:07:56Z","timestamp":1764245276118,"version":"3.46.0"},"reference-count":37,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T00:00:00Z","timestamp":1764201600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The University of Texas MD Anderson Lung Moon Shot Program"},{"name":"The University of Texas MD Anderson Translational Molecular Pathology-Immunoprofiling Lab (TMP-IL) Moon Shots Platform"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>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\u2013Meier 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 &lt; 0.001) were independently associated with MET overexpression. Kaplan\u2013Meier 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, the AIC-selected OS and PFS models both demonstrated that MET overexpression remained a significant prognostic factor (OS: p = 0.010; PFS: p = 0.026). Conclusions: This real-world study suggests that MET overexpression, as assessed by IHC, is associated with better survival in advanced NSCLC patients treated with ICIs, independent of PD-L1 level. These results suggest the potential of MET expression as a predictive marker for ICI efficacy in advanced NSCLC patients and support the combination of MET-targeted agents with anti-PD1\/PD-L1 ICIs as a promising strategy for NSCLC patients with MET overexpression.<\/jats:p>","DOI":"10.3390\/cancers17233801","type":"journal-article","created":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T11:50:13Z","timestamp":1764244213000},"page":"3801","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["MET Overexpression Is Associated with Superior Immunotherapy Benefit in Advanced Non-Small Cell Lung Cancer"],"prefix":"10.3390","volume":"17","author":[{"given":"Hui","family":"Li","sequence":"first","affiliation":[{"name":"Department of Thoracic\/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"},{"name":"Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6553-3279","authenticated-orcid":false,"given":"Lingzhi","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Thoracic\/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pedro","family":"Rocha","sequence":"additional","affiliation":[{"name":"Medical Oncology Department, Hospital del Mar, 08003 Barcelona, Spain"},{"name":"IMIM (Instituto Hospital del Mar de Investigaciones M\u00e9dicas), 08003 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rafael","family":"Bach","sequence":"additional","affiliation":[{"name":"Medical Oncology Department, Hospital del Mar, 08003 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1253-630X","authenticated-orcid":false,"given":"Luisa M.","family":"Solis Soto","sequence":"additional","affiliation":[{"name":"Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Waree","family":"Rinsurongkawong","sequence":"additional","affiliation":[{"name":"Department of Thoracic\/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bingnan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Thoracic\/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7980-0515","authenticated-orcid":false,"given":"Haniel A.","family":"Araujo","sequence":"additional","affiliation":[{"name":"Department of Thoracic\/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasir Y.","family":"Elamin","sequence":"additional","affiliation":[{"name":"Department of Thoracic\/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9229-156X","authenticated-orcid":false,"given":"Mehmet","family":"Altan","sequence":"additional","affiliation":[{"name":"Department of Thoracic\/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, 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