Prevalence, molecular characterization, and prognosis of c-Met protein overexpression in a real-world cohort of patients with non-squamous non-small cell lung cancer

Authors

  • Jair Bar Jusidman Cancer Center, Sheba Medical Center, Ramat Gan, Israel; The Gray Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israe https://orcid.org/0000-0002-1224-3646
  • Mona H. Cai AbbVie, Inc., North Chicago, Illinois, USA
  • Yookyung Christy Choi AbbVie, Inc., North Chicago, Illinois, USA
  • Shobhit Baijal University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
  • Weilong Zhao AbbVie, Inc., North Chicago, Illinois, USA
  • Alexander Liede AbbVie, Inc., North Chicago, Illinois, USA
  • Athan Vasilopoulos AbbVie, Inc., North Chicago, Illinois, USA
  • Lisa Roberts-Rapp AbbVie, Inc., North Chicago, Illinois, USA
  • Fang Jiang AbbVie, Inc., North Chicago, Illinois, USA
  • Archana Simmons AbbVie, Inc., North Chicago, Illinois, USA
  • Christine Ratajczak AbbVie, Inc., North Chicago, Illinois, USA
  • Shun Lu Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China
  • Peter J. Ansell AbbVie, Inc., North Chicago, Illinois, USA
  • D. Ross Camidge University of Colorado Cancer Center, Aurora, Colorado, USA.

DOI:

https://doi.org/10.2340/1651-226X.2025.44344

Keywords:

NSCLC, real-world data, c-Met protein overexpression, MET amplification, Teliso-V

Abstract

Background and purpose: c-Met (also known as MET) protein is encoded by the MET proto-oncogene. In non-small cell lung cancer (NSCLC), c-Met protein overexpression (OE) drives tumorigenesis and is a therapeutic target, given recent US Food and Drug Administration approval of telisotuzumab vedotin-tllv. This retrospective analysis of tumor samples and clinical data from real-world patients with non-squamous NSCLC characterized the prevalence of c-Met protein OE, its association with messenger ribonucleic acid (mRNA) expression, MET gene amplification, programmed-death ligand 1 (PD-L1) expression, and its impact on prognosis.

Patients and methods: A patient cohort was selected for manual abstraction of clinical data from electronic health records. Patients were selected based on the availability of sufficient remnant tissue for biomarker analyses, including c-Met immunohistochemistry (IHC). Comparative assessments were conducted for c-Met protein expression by IHC, MET gene amplification, mRNA expression, and PD-L1 expression levels by IHC.

Results: In total, 305 and 84 patients were included in the biomarker prevalence and outcome analyses, respectively. Overall, c-Met protein OE was detected in 25% of tissue samples. Of the 212 samples with fluorescence in situ hybridization data, MET amplification was seen in 9%. Concordance of c-Met protein OE with MET mRNA levels was observed with area under the concentration-time curve values of 0.738 and 0.736 in MET OE or MET high OE, respectively, using Receiver Operating Characteristic analysis. c-Met protein OE was associated with poor prognosis (unadjusted hazard ratio for death of 2.04).

Interpretation: These data suggest that c-Met protein OE is associated with MET mRNA expression, shows limited overlap with other MET aberrations, and may be linked to poor prognosis in NSCLC.

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References

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Published

2025-11-18

How to Cite

Bar, J., Cai, M. H., Choi, Y. C., Baijal, S., Zhao, W., Liede, A., … Camidge, D. R. (2025). Prevalence, molecular characterization, and prognosis of c-Met protein overexpression in a real-world cohort of patients with non-squamous non-small cell lung cancer. Acta Oncologica, 64, 1544–1553. https://doi.org/10.2340/1651-226X.2025.44344

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Vol. 64 (2025): Acta Oncologica

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Copyright (c) 2025 Jair Bar, Mona H. Cai, Yookyung Christy Choi, Shobhit Baijal, Weilong Zhao, Alexander Liede, Athan Vasilopoulos, Lisa Roberts-Rapp, Fang Jiang, Archana Simmons, Christine Ratajczak, Shun Lu, Peter J. Ansell, D. Ross Camidge

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