Abstract
Background
Mesenchymal epithelial transition (MET) overexpression has been reported in approximately 50–60% of epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancers. However, the prognostic significance of MET overexpression has not been established in advanced lung adenocarcinoma (ADC) patients with EGFR-sensitive mutations.
Methods
A retrospective study was performed on a total of 406 treatment-naïve advanced ADC patients with EGFR mutation detection and MET expression information. EGFR mutations were detected by next‐generation sequencing or amplification refractory mutation system-polymerase chain reaction. Immuno-histochemistry staining of MET expression was evaluated by H-score and overexpression was defined as an H-score ≥ 200. Overall survival (OS) and progression-free survival (PFS) were analyzed according to MET expression.
Results
Among the 406 patients, 208 patients had EGFR mutations, including 102 exon 19_del mutations, 94 L858R mutations and 12 other types of mutations. Of 110 patients with concomitant EGFR mutations and MET overexpression, 61 (59.8%) patients had 19_del mutations, 44 (46.8%) patients had L858R mutations and five (41.7%) patients had others. Patients with MET overexpression had a markedly shorter PFS and OS than patients with MET H-score < 200 in the EGFR L858R mutation subgroup (median PFS: 12 versus 26 months, p = 0.001; median OS: 24 versus 32 months, p = 0.038), whereas no significant difference was observed in 19_del mutation subgroup. Multivariate Cox analysis showed that MET overexpression was an independent poor prognostic factor for PFS and OS in patients with the L858R mutations (HR = 3.064, 95% CI 1.705–5.507, p < 0.001; HR = 2.043, 95% CI 1.000–4.172; p = 0.049), rather than 19_del.
Conclusions
MET overexpression is a poor prognostic factor for advanced ADC patients with the EGFR L858R mutation.
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Funding
This work was supported by the National Natural Science Foundation of China [grant number 82072333 and 81773022]; and the Natural Science Foundation of Hubei Province [grant number 2020CFB808].
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NW contributed to methodology, writing—original draft. YZ contributed to investigation, data curation, formal analysis. YW contributed to methodology, investigation. BH contributed to resources, project administration. JW contributed to resources, project administration. RZ contributed to resources. JF contributed to conceptualization, supervision, project administration. XN contributed to conceptualization, supervision, funding acquisition.
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Approval was obtained from the ethics committee of Tongji Medical College of Huazhong University of Science and Technology, and all patients signed informed consent forms. The procedures used in this study adhere to the tenets of the Declaration of Helsinki.
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Wang, N., Zhu, Y., Wu, Y. et al. MET overexpression in EGFR L858R mutant treatment-naïve advanced lung adenocarcinoma correlated with poor prognosis: a real-world retrospective study. J Cancer Res Clin Oncol 149, 3219–3228 (2023). https://doi.org/10.1007/s00432-022-04225-5
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DOI: https://doi.org/10.1007/s00432-022-04225-5