Lung cancer (LC) cells frequently express programmed death-ligand 1 (PD-L1). Although this expression grossly correlates with likelihood of response to checkpoint inhibitors, prediction of response is rather imperfect and, thus, more accurate predictive biomarkers are mandatory. The aim of this study was to investigate the association of immune checkpoint PD-L1 and DNA methylation status of DNA repair genes (RAD51B and XXRC3) as well as vimentin (VIM) expression in non-small cell lung cancer (NSCLC), correlating with patients' outcome.
A cohort of NSCLC patients diagnosed between August 2014 and June 2017 were enrolled after informed consent. Expression of PD-L1 was determined by IHQ. Evaluation of the methylation status of DNA repair genes (RAD51B and XRCC3) and VIM expression was performed by quantitative methylation-specific PCR (qMSP) using SybrGreen methodology. Predictors of PD-L1 expression were determined using logistic regression multivariable models. Impact on overall survival was determined using Cox analysis.
A total of 75 patients with NSCLC were assessed for PD-L1 immunoexpression, 60 (80%) were male and the median age was 64 years old (range: 29-88). Fifty patients (66.7%) presented adenocarcinoma, 24 (32%) squamous cell carcinoma and one NSCLC NOS. Thirty-nine (52%) cases depicted positivity for PD-L1. RAD51B promoter methylation levels and VIM expression were significantly higher in PD-L1 positive cases compared to negative group (p = 0.01). This significant association was maintained in multivariable analyses: per each unit increase in RAD51B promoter methylation level and VIM expression, the OR for PD-L1 expression was 20.4 (CI95%: 1.5-275.2) and 1.23 (CI95%: 1-1.4), respectively. Association between XXRC3 promoter methylation and PD-L1 expression was not found. None of the analyzed markers associated with patients’ overall survival.
Herein, higher RAD51B methylation levels and VIM expression are independently associated with PD-L1 immunoexpression. Further studies with an extended cohort and follow-up period are warranted to validate these results.
Instituto Português de Oncologia do Porto.
Instituto Português de Oncologia do Porto.
All authors have declared no conflicts of interest.