Genetic Variations in Key MicroRNAs are Associated With the Survival of Nonsmall Cell Lung Cancer.
Genetic Variations in Key MicroRNAs are Associated With the Survival of Nonsmall Cell Lung Cancer.
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关键 MicroRNA 的遗传变异与非小细胞肺癌的生存相关
DOI：
10.1097/md.0000000000002084
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发表时间：
2015-11
期刊：
影响因子：
1.6
通讯作者：
Shen H
中科院分区：
文献类型：
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作者：
Wu S;Shen W;Pan Y;Zhu M;Xie K;Geng L;Wang Y;Liang Y;Xu J;Cao S;Xu W;Chen B;Hu Z;Ma H;Wu J;Shen H
微RNA （micrornas, miRNAs）是一类参与癌变的非编码小RNA分子。已经确定mirna的遗传变异与癌症风险、预后和生存有关。在本研究中，我们在一项包括1001例病例的临床队列研究中调查了几种关键mirna （miR-184、miR-218和miR-124）的单核苷酸多态性（snp）是否与非小细胞肺癌（NSCLC）的预后相关。采用Cox比例风险回归模型估计风险比（hr）及其95%置信区间（ci）。我们发现5个snp与NSCLC生存相关（rs919968、rs3775815、rs4867902和rs6122390在加性模型中：校正HR = 1.15, 95% CI = 1.02-1.29；校正HR = 0.78, 95% CI = 0.67-0.91，校正HR = 1.24, 95% CI = 1.09-1.41；校正HR = 1.21, 95% CI = 1.07-1.36；优势模型中rs298206: HR = 1.25, 95% CI = 1.05-1.49）。即使经过Bonferroni校正，3个snp仍然显著（rs3775815、rs4867902和rs6122390的校正P分别为0.010、0.010和0.032）。此外，对这5个snp的综合分析显示，不利等位基因数目（rs919968-A、rs3775815-C、rs4867902-G、rs6122390-A和rs298206-T）与NSCLC死亡风险之间存在显著的位点剂量效应（P < 0.001）。rs4867902基因型与手术状态之间存在统计学上显著的乘法交互作用（Pint = 0.013）。这些发现表明mirna （miR-184， miR-218和miR-124）的遗传变异可能是NSCLC患者的预后标志物。
AbstractMicroRNAs (miRNAs) are a class of small, noncoding RNA molecules involved in carcinogenesis. It has been identified that genetic variations in miRNAs contribute to cancer risk, prognosis, and survival. In the present study, we investigated whether single nucleotide polymorphisms (SNPs) of several key miRNAs (miR-184, miR-218, and miR-124) were associated with the prognosis of nonsmall cell lung cancer (NSCLC) in a clinical cohort study including 1001 cases. Cox proportional hazards regression models were used to estimate the hazard ratios (HRs) and their 95% confidence intervals (CIs). We found that 5 SNPs were associated with NSCLC survival (rs919968, rs3775815, rs4867902, and rs6122390 in an additive model: adjusted HR = 1.15, 95% CI = 1.02–1.29; adjusted HR = 0.78, 95% CI = 0.67–0.91, adjusted HR = 1.24, 95% CI = 1.09–1.41; adjusted HR = 1.21, 95% CI = 1.07–1.36, respectively; rs298206 in a dominant model: HR = 1.25, 95% CI = 1.05–1.49). Even after the Bonferroni correction, 3 SNPs remained significant (adjusted P = 0.010, 0.010, and 0.032 for rs3775815, rs4867902, and rs6122390, respectively). Additionally, the combined analysis of these 5 SNPs showed a significant locus-dosage effect between number of unfavorable alleles (rs919968-A, rs3775815-C, rs4867902-G, rs6122390-A, and rs298206-T) and death risk of NSCLC (P for trend < 0.001). A statistically significant multiplicative interaction was found between the genotypes of rs4867902 and surgical operation status (Pint = 0.013). These findings indicated that genetic variations in miRNAs (miR-184, miR-218, and miR-124) might be prognostic markers for NSCLC patients.