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.