Guo Zhen, Wang Youhong, Zhao Yu, Jin Yi, An Liang, Wu Bin, Liu Zhaoqian, Chen Xiaoping, Zhou Honghao, Wang Hui, Zhang Wei
Department of Clinical Pharmacology, Xiangya Hospital, Central South University and Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, 410008, P.R. China.
Key Laboratory of Translational Radiation Oncology, Hunan Province, Department of Radiation Oncology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, P.R. China.
Oncotarget. 2017 Jul 31;8(37):62286-62297. doi: 10.18632/oncotarget.19725. eCollection 2017 Sep 22.
LncRNA 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 in nasopharyngeal carcinoma (NPC) remains elusive. The objective of the present study was to evaluate the effect of single nucleotide polymorphisms (SNPs) in on treatment efficacy and toxicity in NPC patients receiving chemoradiotherapy. Three potentially functional SNPs of 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 GA 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.
长链非编码RNA（LncRNA）在多种人类癌症中发挥着肿瘤抑制作用，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，其在鼻咽癌（NPC）中的作用仍不明确。本研究的目的是评估[具体基因名称]中单核甘酸多态性（SNP）对接受放化疗的鼻咽癌患者治疗疗效和毒性的影响。对267例鼻咽癌患者的[具体基因名称]的三个潜在功能性SNP进行基因分型，并在另外238例来自中国南方接受放化疗的鼻咽癌患者中进行验证。采用多因素逻辑回归分析和分层分析来评估候选SNP与放化疗疗效及毒性反应之间的关联。我们的结果显示，在发现集（OR = 2.403，P = 0.009；OR = 2.454，P = 0.015）、验证集（OR = 3.653，P = 0.027；OR = 4.767，P = 0.016）以及合并数据集（OR = 1.880，P = 0.007；OR = 2.079，P = 0.005）中，rs2067079与严重骨髓抑制和严重中性粒细胞减少一直保持着相关性。在以紫杉醇+铂类作为同步放化疗方案的亚组中，rs2067079 CT基因型携带者出现严重骨髓抑制（OR = 3.878，P = 0.003）和严重中性粒细胞减少（OR = 3.794，P = 0.009）的风险甚至更高。此外，我们发现rs6790存在基因剂量效应，对于rs6790 GG、GA、AA基因型携带者，严重骨髓抑制的发生率分别从23.56%降至17.21%再降至10%，严重中性粒细胞减少的发生率分别从30.4%降至20.9%再降至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诱导毒性反应的预测生物标志物具有潜在作用。
