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

Abstract

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.

Association between PD-1 and PD-L1 Polymorphisms and the Risk of Cancer: A Meta-Analysis of Case-Control Studies

“…It has been proposed that gene expression could be potentially affected by genetic polymorphisms [21,61,62,63]. Alterations in the expression of PD-1 and PDL-1 were detected in many cancer types including gastric cancer, lung cancer, thyroid cancer, laryngeal carcinoma, extrapulmonary small cell carcinoma, and breast cancer [63,64,65,66,67,68,69].…”

Recent Findings in the Regulation of Programmed Death Ligand 1 Expression

“…Kogure and Kataoka (59) also reported that structural variants induce PD-L1 overexpression in ATL. More recently, a study in gastric cancer has revealed that PD-L1 rs2297136 AA+AG genotype, a new polymorphism in 3′-UTR of PD-L1 , is also correlated with the positive protein expression of PD-L1 (60).…”

Clinicopathological and Prognostic Significance of Immunoscore and PD-L1 in Intrahepatic Cholangiocarcinoma

“…Emerging clinical data have shown that the upregulation of PD-L1 in multiple tumor types has prognostic implication and can predict the clinical response to PD-1 blockade therapy. 12,13 Although the potential clinical relevance of PD-L1 expression in ICC has already been reported in several previous studies, the prognostic value of PD-L1 for ICC is still controversial. [14][15][16][17] This study aimed to examine the clinicopathological and prognostic roles of T-lymphocyte-based IS, following similar principles described by Galon et al in ICC.…”