Expression of PD-L1, cancer stem cell and epithelial-mesenchymal transition phenotype in non-small cell lung cancer

The purpose of this study was to investigate the expression of PD-L1, cancer stem cells (CSC) markers (CD44, NANOG, and ALDH1) and epithelial-mesenchymal transition (EMT) markers and to evaluate their correlation and prognostic significance in non-small cell lung cancer (NSCLC) patients. PD-L1 protein expression was evaluated in resected 277 NSCLC cases and its correlation with CSC and EMT marker expression and survival was determined based on immunohistochemical (IHC) analysis. mRNA expression obtained from The Cancer Genome Atlas and the Kaplan-Meier plotter database were compared with the IHC results. PD-L1 expression was negatively correlated with ALDH1 expression in adenocarcinoma by IHC and mRNA expression. PD-L1 expression was also associated with mesenchymal phenotype (vimentin and TWIST) adenocarcinoma by IHC and mRNA expression. PD-L1 expression was associated with poor prognosis in adenocarcinoma by IHC. However, NANOG or ALDH1 expression measured by IHC and mRNA expression was correlated with a favourable prognosis in adenocarcinoma. Epithelial marker p120-catenin detected by IHC and mRNA expression was associated with a favourable prognosis in adenocarcinoma, however mesenchymal marker TWIST was associated with a worse prognosis. Patients with low PD-L1 and high ALDH1 expression showed more favourable prognoses than adenocarcinoma patients with other expression patterns. In multivariate analysis, ALDH1 detected by IHC and mRNA expression was an independent favourable prognostic marker for adenocarcinoma. Our study results support the hypothesis that PD-L1 interacts with CSC and EMT features and that PD-L1, ALDH1, and the mesenchymal phenotype may serve as tandem markers as prognostic factor in NSCLC.