Age-related common miRNA polymorphism associated with severe toxicity in lung cancer patients treated with platinum-based chemotherapy
Age-related common miRNA polymorphism associated with severe toxicity in lung cancer patients treated with platinum-based chemotherapy
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年龄相关的常见 miRNA 多态性与接受铂类化疗的肺癌患者的严重毒性相关
DOI：
10.1111/1440-1681.12704
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发表时间：
2017-12-01
影响因子：
2.9
通讯作者：
Liu, Zhao-Qian
中科院分区：
文献类型：
--
作者：
Fang, Chao;Li, Xiang-Ping;Liu, Zhao-Qian
铂类化疗的毒性严重阻碍了肺癌患者的成功治疗。microRNAs（miRs）对肺癌的发生和生存率有重要影响。本研究的目的是探讨常见的miRNA变异体与肺癌患者铂类化疗毒性之间的关系。采用MALDI-TOF质谱技术对408例肺癌患者的8个miRNA功能性单核苷酸多态性（SNP）进行基因分型。所有患者均经组织学确诊为肺癌，并接受以铂类为基础的化疗至少2个周期。结果发现，miR-5197的多态性rs 2042553在加性（P= 0.031，比值比[OR]=1.41，95%置信区间[CI] 1.03-1.93）和显性（P= 0.009，OR=1.80，95% CI 1.16-2.80）模型中与总体严重毒性显著相关。在显性模型中，miR-605 rs 2043556与重度肝毒性显著相关（P= 0.022，OR=2.51，95% CI 1.12-4.14）。此外，miR-146 a的rs 2910164在累加模型中对重度肝毒性具有边际统计学效应（P=.054）。亚组分析显示，在年龄> 56岁、吸烟和不吸烟患者中，miR-27 a rs 895819与胃肠道毒性相关。综上所述，我们的研究结果显示miR-5197、miR-605、miR-146 a和miR-27 a的多态性与肺癌化疗毒性有关，这可能作为肺癌患者铂类化疗毒性评价的预测工具。
Platinum-based chemotherapy toxicity severely impedes successful treatment in lung cancer patients. MicroRNAs (miRs) have a significant impact on the occurrence and survival rate of lung cancer. The purpose of this study was to investigate the association between common miRNA variants and platinum-based chemotherapy toxicity in lung cancer patients. A total of eight functional single nucleotide polymorphisms (SNPs) of miRNA were genotyped in 408 lung cancer patients by MALDI-TOF mass spectrometry. All the patients were histologically confirmed as lung cancer, and were treated with platinum-based chemotherapy for at least two cycles. It was found that the polymorphism rs2042553 of miR-5197 had a significant association with overall severe toxicity in both additive (P=.031, odds ratio [OR]=1.41, 95% confidence interval [CI] 1.03-1.93) and dominant (P=.009, OR=1.80, 95% CI 1.16-2.80) models. MiR-605 rs2043556 was significantly related to severe hepatotoxicity in dominant model (P=.022, OR=2.51, 95% CI 1.12-4.14). In addition, rs2910164 of miR-146a had marginal statistical effect on severe hepatotoxicity in additive model (P=.054). The subgroup analyses showed that miR-27a rs895819 was related to gastrointestinal toxicity in age >56years old, smoking and non-smoking patients. Taken together, our results revealed that polymorphisms of miR-5197, miR-605, miR-146a, and miR-27a contributed to the chemotherapy toxicity of lung cancer, which may serve as a predictive tool for toxicity evaluation of platinum-based chemotherapy in lung cancer patients.