Genetic polymorphisms of long non-coding RNA GAS5 predict platinum-based concurrent chemoradiotherapy response in nasopharyngeal carcinoma patients.
Genetic polymorphisms of long non-coding RNA GAS5 predict platinum-based concurrent chemoradiotherapy response in nasopharyngeal carcinoma patients.
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长链非编码RNA GAS5的基因多态性预测鼻咽癌患者铂类同步放化疗的反应
DOI：
10.18632/oncotarget.19725
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发表时间：
2017-09-22
期刊：
影响因子：
--
通讯作者：
Zhang W
中科院分区：
文献类型：
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作者：
Guo Z;Wang Y;Zhao Y;Jin Y;An L;Wu B;Liu Z;Chen X;Zhou H;Wang H;Zhang W
LncRNA GAS5 在多种人类癌症中发挥肿瘤抑制作用，有望成为一种新型的诊断生物标志物、治疗靶点以及预后生物标志物。然而，GAS5 在鼻咽癌 (NPC) 中的作用仍不清楚。本研究的目的是评估 GAS5 中的单核苷酸多态性 (SNP) 对接受放化疗的鼻咽癌患者的治疗效果和毒性的影响。在 267 名鼻咽癌患者中对 GAS5 的三个潜在功能性 SNP 进行了基因分型，并在另外 238 名来自中国南方接受放化疗的鼻咽癌患者中进行了验证。使用多变量逻辑回归分析和分层分析来评估候选SNP与放化疗疗效和毒性反应的关联。我们的结果表明，rs2067079 在发现集（分别为 OR=2.403，P=0.009；OR=2.454，P=0.015）、验证集（分别为 OR=3.653，P=0.027；OR=4.767，P=0.016）和组合数据集中与严重骨髓抑制和严重中性粒细胞减少症保持一致的关联（OR=1.880，P=0.007；OR=2.079，P=0.005；分别）。 rs2067079 CT基因型携带者在采用紫杉醇+铂作为同步放化疗方案的亚组中，严重骨髓抑制（OR=3.878，P=0.003）和严重中性粒细胞减少（OR=3.794，P=0.009）的风险更加显着增加。此外，我们发现rs6790存在基因效应，rs6790 GG、GA、AA基因型携带者的严重骨髓抑制发生率从23.56%下降到17.21%到10%，严重中性粒细胞减少发生率从30.4%下降到20.9%到17.1%。我们的结果表明，lncRNA GAS5 多态性 rs2067079 和 rs6790 作为鼻咽癌患者放化疗引起的毒性反应的预测生物标志物的潜在作用。
LncRNA GAS5 plays a tumor suppressive role in a variety of human cancers and promises to be a novel diagnostic biomarker, therapy target, as well as prognostic biomarker. However, the role of GAS5 in nasopharyngeal carcinoma (NPC) remains elusive. The objective of the present study was to evaluate the effect of single nucleotide polymorphisms (SNPs) in GAS5 on treatment efficacy and toxicity in NPC patients receiving chemoradiotherapy. Three potentially functional SNPs of GAS5 were genotyped in 267 NPC patients and validated in another 238 NPC patients treated with chemoradiotherapy from southern China. Multivariate logistic regression analyses and stratification analyses were used to estimate the association of candidate SNPs and chemoradiotherapy efficacy and toxic reactions. Our results showed that rs2067079 kept a consistent association with severe myelosuppression and severe neutropenia in discovery set (OR=2.403, P=0.009; OR=2.454, P=0.015; respectively), validation set (OR=3.653, P=0.027; OR=4.767, P=0.016; respectively), and combined dataset (OR=1.880, P=0.007; OR=2.079, P=0.005; respectively). rs2067079 CT genotype carriers presented an even more remarkable increased risk of severe myelosuppression (OR=3.878, P=0.003) and severe neutropenia (OR=3.794, P=0.009) in subgroups taking paclitaxel+platinum as concurrent chemoradiotherapy regimen. Besides, we found a gene-does effect of rs6790, with the incidence rate of severe myelosuppression decreased from 23.56% to 17.21% to 10% and the incidence rate of severe neutropenia decreased from 30.4% to 20.9% to 17.1% for rs6790 GG vs GA vs AA genotype carriers. Our results indicate the potential role of lncRNA GAS5 polymorphisms rs2067079 and rs6790 as predictive biomarkers for chemoradiotherapy induced toxic reactions in NPC patients.