Cytoplasmic YAP Expression is Associated with Prolonged Survival in Patients with Lung Adenocarcinomas and Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Treatment
Yes-associated protein (YAP) has been reported to be associated with the prognosis of various cancers and also to affect epidermal growth factor receptor–tyrosine kinase inhibitor (EGFR–TKI) activity in ovarian cancer cell lines. However, few studies have evaluated YAP protein expression in lung cancer, and the results have lacked consistency.
YAP expression was evaluated in a total of 205 curatively resected lung adenocarcinomas and 36 cases of EGFR-mutated TKI-treated patients. Correlations between the expression of YAP and clinicopathologic features, response to EGFR–TKI treatment, and prognostic significance were analyzed.
High cytoplasmic YAP expression was positively correlated with the clinicopathologic parameters that have been associated with favorable prognosis. Multivariate analysis revealed that high cytoplasmic YAP expression was an independent prognostic factor in lung adenocarcinomas (progression-free survival: hazard ratio [HR] 0.659; 95 % confidence interval [CI] 0.431–1.010; p = 0.050; overall survival: HR, 0.474; 95 % CI 0.263–0.854; p = 0.013) and EGFR-TKI-treated patients with EGFR mutation (progression-free survival: HR, 0.346; 95 % CI 0.146–0.818; p = 0.016; overall survival: HR, 0.291; 95 % CI 0.125–0.676; p = 0.004).
High cytoplasmic YAP expression predicted a good clinical outcome for patients with lung adenocarcinoma and in EGFR–TKI-treated patients. Therefore, YAP may play a role in EGFR–TKI-treated lung cancer, and YAP targeting may enhance therapeutic effects in combination with other cancer drugs.
KeywordsOverall Survival Gefitinib Erlotinib Lung Adenocarcinoma EGFR Mutation
Supported in partly by Grants from the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2013-059757 to J.H.C. and 2011-0025344 to J.E.K.). The authors are indebted to J. Patrick Barron, professor emeritus, Tokyo Medical University, and adjunct professor, Seoul National University Bundang Hospital, for his pro bono editorial work.
The authors declare no conflict of interest.
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