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

Publication date: 30 January 2017
Source:Gene, Volume 599
Author(s): 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
IntroductionThis study was conducted to investigate whether polymorphisms of genes involved in immune checkpoints can predict the prognosis of patients with early stage non-small cell lung cancer (NSCLC) after surgical resection.Materials and methodsTwelve single nucleotide polymorphisms (SNPs) of PD-1, PD-L1, and CTLA-4 genes were selected and genotyped. A total of 354 patients with early stage NSCLC who underwent curative surgical resection were enrolled. The association of the SNPs with overall survival (OS) was analyzed.ResultsAmong the 12 SNPs investigated, PD-L1 rs4143815C>G, rs822336G>C, and rs822337T>A were significantly associated with worse survival outcomes in multivariate analyses. When the 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 transcription activity compared with C allele (P=0.001), and the rs822336C-rs822337A haplotype had a decreased promoter activity compared with the rs822336G-rs822337T haplotype (P=0.004). Patients with higher expression of PD-L1 mRNA had a better survival compared with lower expression (P=0.03).ConclusionsPD-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.



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