Abstract 1987
Background
Enhancer of zeste homolog 2 (EZH2) is reported to be involved in lung cancer pathogenesis via the epigenetic regulation of various genes. Recently, EZH2 was shown to control mechanisms of adaptive resistance to immunotherapy in melanoma; however, the association between EZH2 and programmed death-ligand 1 (PD-L1), which reflects the tumor microenvironment, remains poorly understood.
Methods
A total of 428 patients with resected lung adenocarcinoma were analyzed for their EZH2 and PD-L1 expression by immunohistochemistry and evaluated to determine the association between the EZH2 and PD-L1 expression.
Results
Among 428 patients, the EZH2 expression was identified in 219 (51.2%), while the PD-L1 expression was observed in 88 (20.6%). The recurrence-free and overall survival (RFS and OS, respectively) were significantly shorter in patients with the EZH2 expression than in those without it. A multivariate analysis showed that EZH2 remained an independent prognosticator for the RFS and OS. Patients with the EZH2-positive lung adenocarcinoma exhibited a significantly higher expression of PD-L1 than those without it. A logistic regression analysis with backward elimination revealed that the presence of lymphatic and vessel invasion and PD-L1 positivity were independently associated with the EZH2 expression, while age over 70, the presence of vessel invasion, wild-type epidermal growth factor receptor, and EZH2 positivity were significantly associated with the PD-L1 expression.
Conclusions
EZH2-expressing lung adenocarcinomas were shown to express PD-L1 protein more frequently than non-expressing lesions. This study provides the first evidence of a possible association between the EZH2 and PD-L1 expression in patients with resected lung adenocarcinoma.
Clinical trial identification
Legal entity responsible for the study
Gouji Toyokawa.
Funding
Japan Society for the Promotion of Science and Kaibara Morikazu Medical Science Promotion Foundation.
Editorial Acknowledgement
Disclosure
All authors have declared no conflicts of interest.