Prognostic implication of PD-L1 polymorphisms in non-small cell lung cancer treated with radiotherapy

Background: To investigate the impact of programmed death-ligand 1 (PD-L1) polymorphisms on the prognosis of non-small cell lung cancer (NSCLC) patients treated with curative radiotherapy. Methods: Four single nucleotide polymorphisms (SNPs) (rs822336G>C, rs822337T>A, rs822338C>T, and rs2297136A>G) in the PD-L1 gene were evaluated in 124 NSCLC patients. Clinical stage was I in 28, II in 17, and III in 79 patients. Fifty-seven patients received radiotherapy alone, including 28 patients who received stereotactic body radiotherapy. Sixty-seven patients received sequential or concurrent chemoradiotherapy. Risk factors for survival outcomes were analyzed with the log-rank test and multivariate Cox proportional hazards models. Results: The rs822336GC+CC genotype was associated with better overall survival (OS) (hazard ratio [HR] = 0.60, 95% confidence interval [CI] = 0.37–0.97, p = 0.036) and regional failure-free survival (RFFS) (HR = 0.32, 95% CI = 0.14–0.76, p = 0.009), compared with rs822336GG genotype. The rs822337TA+AA genotype was associated with better OS (HR =0.54, 95% CI = 0.34–0.88, p = 0.014), progression-free survival (PFS) (HR = 0.64, 95% CI = 0.41–0.99, p = 0.046), and RFFS (HR = 0.38, 95% CI = 0.17–0.81, p = 0.013), compared with rs822337TT genotype. Three SNPs (rs822336, rs822337, and rs822338) were in linkage disequilibrium. Combined GTC and GTT (GT*) haplotype was associated with significantly worse OS (p = 0.018), PFS (p = 0.044), and RFFS (p = 0.038), compared with those with other combined haplotypes. Patients with diplotypes of two GT* haplotypes showed significantly worse OS (p = 0.023) and RFFS (p = 0.014) than those with other diplotypes. Conclusions: These findings suggest that PD-L1 polymorphisms could be predictive markers for NSCLC patients receiving radiotherapy.