Influence of programmed death ligand-1-gene polymorphism rs822336 on the prognosis and safety of postoperative patients with NSCLC who received platinum-based adjuvant chemotherapy

Abstract

Purpose: This study was done to investigate the influence of PDL1-gene polymorphism on the prognosis and safety of postoperative patients with non–small cell lung cancer (NSCLC) who had received platinum-based adjuvant chemotherapy. Methods: A total of 289 postoperative patients with NSCLC who had received platinumbased adjuvant chemotherapy from January 2012 to June 2019 participated in this study. Recurrence status and adverse reactions were documented during adjuvant chemotherapy. Overall survival (OS) data were obtained through telephone follow-up. DNA extracted from hematologic specimens was genotyped for PDL1-gene polymorphism. Associations between genotype status and prognosis were assessed using Kaplan–Meier survival analysis, and multivariate adjustment was performed using Cox regression analysis. Results: Median disease-free survival of the 289 patients with NSCLC was 3.3 years and median OS 4.9 years. With regard to the PDL1 gene polymorphism, only rs822336 was of clinical significance in the subsequent analysis. The minor-allele frequency of rs822336 was 0.21, and distribution of the three genotypes was in accordance with the Hardy–Weinberg equilibrium (P=0.807). Survival analysis according to genotype status suggested that median disease-free survival of patients with GG and GC/CC genotypes was 2.8 and 4.1 years, respectively (P=0.01). Median OS of patients with GG and GC/CC genotypes was 4.1 and 5.4 years, respectively (P=0.008). However, the safety analysis failed to find a significant association between the polymorphism and adverse reactions. Interestingly, expression analysis of RNA extracted from peripheral blood mononuclear cells indicated that PDL1-mRNA expression of patients with the GG genotype was significantly higher than for the GC/CC genotype (P<0.001). Conclusion: The prognosis of postoperative patients with NSCLC who have received platinum-based adjuvant chemotherapy may be influenced by the rs822336 polymorphism through mediation of the mRNA expression of PDL1.