Association of positively selected eIF3a polymorphisms with toxicity of platinum-based chemotherapy in NSCLC patients
Association of positively selected eIF3a polymorphisms with toxicity of platinum-based chemotherapy in NSCLC patients
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NSCLC患者中阳性选择的eIF3a多态性与铂类化疗毒性的关联
DOI：
10.1038/aps.2014.160
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发表时间：
2015-03-01
影响因子：
8.2
通讯作者：
Liu, Zhao-qian
中科院分区：
文献类型：
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作者：
Yin, Ji-ye;Meng, Xiang-guang;Liu, Zhao-qian
目的：真核翻译起始因子3亚基A（eIF3a）在调节蛋白质翻译起始过程中发挥着关键作用，并且eIF3a在肺癌中高表达。在本研究中，我们研究了中国非小细胞肺癌（NSCLC）患者中阳性选择的eIF3a位点SNP与铂类化疗的反应和毒性的关系。方法：从HapMap数据库下载eIF3a位点的SNP数据。对每个 SNP、单倍型、LD 谱和群体分化进行了分析。采用长程单倍型 (LRH) 测试来鉴定 eIF3a 的阳性选择 SNP。总共招募了 325 名 NSCLC 患者，并对这些 SNP 进行了基因分型。结果：5 个阳性选择的 SNP（rs1409314、rs4752219、rs4752220、rs7091672 和 rs10510050）和 5 个非阳性选择的 SNP（rs10886342、rs11198804、 LRH 测试中鉴定出 rs2275112、rs10787899 和 rs4752269）。然而，它们均与铂类化疗反应无关。相反，阳性选择的 SNP 中的 4 个（rs1409314、rs4752219、rs4752220 和 rs7091672）与测试的毒性（中性粒细胞减少、贫血、血小板减少、呕吐和肝毒性）显着相关。此外，rs10510050与血小板减少、呕吐和肝毒性显着相关。 5个非阳性选择的SNP均与5种毒性无关。结论：eIF3a阳性选择的SNP与中国NSCLC患者铂类化疗毒性显着相关。
Aim:Eukaryotic translation initiation factor 3 subunit A (eIF3a) plays critical roles in regulating the initiation of protein translation, and eIF3a is highly expressed in lung cancer. In this study, we investigated the association of the positively selected SNPs of eIF3a with the response to and toxicity of platinum-based chemotherapy in Chinese patients with non-small cell lung cancer (NSCLC).Methods:SNP data for eIF3a locus were downloaded from HapMap database. For each SNP, haplotype, LD profile and population differentiation were analyzed. The long-range haplotype (LRH) test was employed to identify positively selected SNPs of eIF3a. A total of 325 NSCLC patients were enrolled and genotyped for these SNPs.Results:Five positively selected (rs1409314, rs4752219, rs4752220, rs7091672 and rs10510050) and 5 non-positively selected SNPs (rs10886342, rs11198804, rs2275112, rs10787899 and rs4752269) were identified in the LRH test. However, none of them was correlated with the platinum-based chemotherapy response. In contrast, 4 of the positively selected SNPs (rs1409314, rs4752219, rs4752220 and rs7091672) were significantly correlated with the toxicities tested (neutropenia, anemia, thrombocytopenia, emesis and hepatotoxicity). In addition, rs10510050 was significantly correlated with thrombocytopenia, emesis and hepatotoxicity. None of the 5 non-positively selected SNPs was correlated with the 5 toxicities.Conclusion:The positively selected SNPs of eIF3a are significantly correlated with platinum-based chemotherapy toxicities in Chinese NSCLC patients.