Functional polymorphisms in PD-L1 gene are associated with the prognosis of patients with early stage non-small cell lung cancer
Functional polymorphisms in PD-L1 gene are associated with the prognosis of patients with early stage non-small cell lung cancer
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DOI：
10.1016/j.gene.2016.11.007
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发表时间：
2017-01-30
期刊：
影响因子：
3.5
通讯作者：
Park, Jae Yong
中科院分区：
文献类型：
--
作者：
Lee, Shin Yup;Jung, Deuk Kju;Park, Jae Yong
简介：本研究旨在探讨免疫检查点相关基因多态性是否能预测早期非小细胞肺癌（NSCLC）患者手术切除后的预后。材料和方法：选择PD-1、PD-L1和CTLA-4基因12个单核苷酸多态性（SNP）进行基因分型。共入组了354例接受根治性手术切除的早期NSCLC患者。结果：多因素分析显示，PD-L1基因rs 4143815 C>G、rs 822336 G>C和rs 822337 T>A多态性与总生存期（OS）显著相关。当三种SNP组合时，随着不良基因型数量的增加，OS以剂量依赖性方式降低（P趋势= 0.0003）。在荧光素酶检测中，rs 4143815 G等位基因的转录活性低于C等位基因（P = 0.001），rs 822336 C-rs 822337 A单倍型的启动子活性低于rs 822336 G-rs 822337 T单倍型（P = 0.004）。结论：PD-L1基因多态性对手术切除的非小细胞肺癌患者的预后有一定的预测价值。需要进一步的研究来证实我们的发现，并了解PD-L1在NSCLC抗肿瘤免疫和预后中的作用。(C)2016由Elsevier B. V.出版
Introduction: This 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 methods: Twelve 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.Results: Among 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 (P-trend = 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).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. (C) 2016 Published by Elsevier B.V.