Functional polymorphisms in PD-L1 gene are associated with the prognosis of patients with early stage non-small cell lung cancer

Introduction: This study was conducted to investigate whether polymorphisms of genes involved in immune checkpoints can predict the prognosis of patients with early stage non-small cell lung cancer (NSCLC) after surgical resection. Materials and methods: Twelve single nucleotide polymorphisms (SNPs) of PD-1, PD-L1, and CTLA-4 genes were selected and genotyped. A total of 354 patients with early stage NSCLC who underwent curative surgical resection were enrolled. The association of the SNPs with overall survival (OS) was analyzed. Results: Among the 12 SNPs investigated, PD-L1 rs4143815C>G, rs822336G>C, and rs822337T>A were significantly associated with worse survival outcomes in multivariate analyses. When the three SNPs were combined, OS decreased in a dose-dependent manner as the number of bad genotypes increased (P-trend = 0.0003). In the luciferase assay, rs4143815 G allele exhibited a decreased transcription activity compared with C allele (P = 0.001), and the rs822336C-rs822337A haplotype had a decreased promoter activity compared with the rs822336G-rs822337T haplotype (P = 0.004). Patients with higher expression of PD-L1 mRNA had a better survival compared with lower expression (P = 0.03). Conclusions: PD-L1 polymorphisms may be useful for the prediction of prognosis in patients with surgically resected NSCLC. Further studies are needed to confirm our findings and to understand the role of PD-L1 in the antitumor immunity and prognosis in NSCLC. (C) 2016 Published by Elsevier B.V.