Gene, 2017, 01, 28─35, DOI: https://doi.org/doi: 10.1016/j.gene.2016.11.007

Functional polymorphisms in PD-L1 gene are associated with the prognosis of patients with early stage non-small cell lung cancer

Shin Yup Lee, Deuk Kju Jung; Jin Eun Choi; Cheng Cheng Jin; Mi Jeong Hong; Sook Kyung Do; Hyo-Gyoung Kang; Won Kee Lee; Yangki Seok; Eung Bae Lee; Ji Yun Jeong; Kyung Min Shin; Seung Soo Yoo; Jaehee Lee; Seung Ick Cha; Chang Ho Kim; Jae Yong Park

Abstract

Introduction
This study was conducted to investigate whether polymorphisms of genes involved in immune checkpoints can predict the prognosis of patientswith early stage non-small cell lung cancer (NSCLC) after surgical resection.
Materials and methods
Twelve single nucleotide polymorphisms (SNPs) of PD-1, PD-L1, andCTLA-4 geneswere selected and genotyped. A total of 354 patients with early stage NSCLCwho underwent curative surgical resection were enrolled. The association of the SNPs with overall survival (OS) was analyzed.
Results
Among the 12 SNPs investigated, PD-L1 rs4143815CNG, rs822336GNC, and rs822337TNA were significantly associated withworse survival outcomes inmultivariate analyses. Whenthe three SNPs were combined,OS decreased in a dose-dependent manner as the number of bad genotypes increased (Ptrend = 0.0003). In the luciferase assay, rs4143815 G allele exhibited a decreased tranion activity compared with C allele (P = 0.001), and the rs822336C-rs822337A haplotype had a decreased promoter activity comparedwith the rs822336G-rs822337T haplotype (P=0.004). Patientswith higher expression of PD-L1 mRNA had a better survival compared with lower expression (P=0.03).
Conclusions
PD-L1 polymorphisms may be useful for the prediction of prognosis in patients with surgically resected NSCLC. Further studies are needed to confirm our findings and to understand the role of PD-L1 in the antitumor immunity and prognosis in NSCLC.

• DOI: https://doi.org/doi: 10.1016/j.gene.2016.11.007
• ISBN or ISSN: 0378-1119

• 본 연구는 질병관리본부 연구개발과제(과제번호 2017-보건의료생물자원종합관리) 연구비를 지원받아 수행되었습니다.
• This research was supported by a fund(code 2017-보건의료생물자원종합관리) by Research of Korea Centers for Disease Control and Prevention.