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.