The A/G allele of eIF3a rs3740556 predicts platinum-based chemotherapy resistance in lung cancer patients
The A/G allele of eIF3a rs3740556 predicts platinum-based chemotherapy resistance in lung cancer patients
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eIF3a rs3740556 的 A/G 等位基因预测肺癌患者对铂类化疗的耐药性
DOI：
10.1016/j.lungcan.2012.10.005
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发表时间：
2013-01-01
期刊：
影响因子：
5.3
通讯作者：
Liu, Zhaoqian
中科院分区：
文献类型：
--
作者：
Xu, Xiaojing;Han, Lifang;Liu, Zhaoqian
EIF3a是真核细胞翻译起始因子3的最大亚基，被认为影响肿瘤的进展和导致铂耐药的核苷酸切除修复途径的活性。本研究的目的是研究eIF3a基因启动子和外显子区域的可能突变，并评估eIF3a突变状态是否对铂类化疗肺癌患者的预后和预测有意义。771例肺癌患者入选并随访。这些患者是新诊断的偶发肺癌，经组织学或细胞学证实，并接受了至少两个周期的铂类化疗。发现了3个新的eIF3a突变，包括内含子6的11279G和Gt；A、外显子9的Arg438Lys和内含子15的29671G和Gt；A，其等位基因频率分别为0.16、0.18、0.16。携带rs3740556基因的A携带者对铂类药物的化疗反应明显更好(p<；0.05)，而且寿命似乎更长。EIF3a基因多态性可作为铂类药物化疗前评估的预测工具。携带rs3740556 A等位基因的肺癌患者在接受以铂为基础的化疗后往往有良好的预后。(C)2012爱思唯尔爱尔兰有限公司。保留所有权利。
eIF3a is the largest subunit of eukaryotic translation initiation factor 3, which has been suggested to affect tumor progression and activity of nucleotide excision repair pathway contributing to platinum resistance. The purpose of this study was to investigate possible mutations in promoter and exon regions of eIF3a gene and to assess whether eIF3a mutation status have prognostic and predictive significance in platinum-based chemotherapeutic lung cancer patients. 771 lung cancer patients were enrolled and followed up. These patients were newly diagnosed with incident lung cancer, which was confirmed histologically or cytologically, and accepted platinum-based chemotherapy for at least two cycles. Three novel mutations of eIF3a were found, including 11279G > A in intron 6, Arg438Lys in exon 9, 29671G > A in intron 15, with minor allele frequency of 0.16, 0.18, 0.16, respectively. A-carrier patients of rs3740556 conferred a significantly better platinum-based chemotherapy response (p < 0.05) and seemed to live longer. eIF3a genetic polymorphisms can be considered as predictive tools for pretreatment evaluation of platinum-based chemotherapy. Lung cancer patients carrying rs3740556 A allele tended to have a favorable prognosis after treatment with platinum-based chemotherapy. (C) 2012 Elsevier Ireland Ltd. All rights reserved.