Polymorphism of the programmed death‐ligand 1 gene is associated with its protein expression and prognosis in gastric cancer

BACKGROUND AND AIM: While the incidence and mortality of gastric cancer (GC) remains high, and prognosis of GC remains poor, molecules in programmed death-1 (PD-1), programmed death-ligand 1 (PD-L1), and programmed death-ligand 2 (PD-L2) pathway are promising prognostic biomarker of GC. The polymorphisms on PD-1, PD-L1, and PD-L2 may be associated with their protein expressions and affect the survival of GC patient. METHODS: Seven hundred fifty-six GC patients who voluntarily supplied blood samples were enrolled in our study. We genotyped nine polymorphisms on PD-1, PD-L1, and PD-L2, then evaluated the association of the single nucleotide polymorphisms with GC prognosis and analyzed the relationship between the PD-1, PD-L1, and PD-L2 single nucleotide polymorphism genotypes and their protein expression. RESULTS: We found that PD-L1 rs822336 CC genotype was independently associated with a better survival of all GC patients and those without postoperative chemotherapy (hazard ratio [HR] = 0.504, 95% confidence interval [CI] = 0.283-0.897 and HR = 0.385, 95% CI = 0.189-0.786). AA+AG genotype of rs2297136 in 3'UTR of the PD-L1 was correlated with the protein expression of PD-L1 protein both in patients overall and those without postoperative chemotherapy (P = 0.013 and P = 0.012). AA+AG genotype of rs2297136 served as an independent factor of better prognosis in patients without postoperative chemotherapy (HR = 0.348, 95% CI = 0.125-0.968). CONCLUSIONS: Overall, PD-L1 polymorphisms and protein expression were associated with the prognosis of patients with GC.