A microRNA-135a/b binding polymorphism in CD133 confers decreased risk and favorable prognosis of lung cancer in Chinese by reducing CD133 expression
A microRNA-135a/b binding polymorphism in CD133 confers decreased risk and favorable prognosis of lung cancer in Chinese by reducing CD133 expression
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CD133 中的 microRNA-135a/b 结合多态性可通过降低 CD133 表达来降低中国人患肺癌的风险和良好的预后
DOI：
10.1093/carcin/bgt181
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发表时间：
2013-10-01
期刊：
影响因子：
4.7
通讯作者：
Lu, Jiachun
中科院分区：
文献类型：
--
作者：
Cheng, Mei;Yang, Lei;Lu, Jiachun
CD133是肿瘤干细胞(CSCs)的重要标志，参与肿瘤的发生和发展。最近的研究证实CD133是癌症的一个预后因素，这取决于它的表达和基因变异。在这里，我们假设CD133的单个核多态(SNPs)可能与肺癌风险和预后相关。基于三个独立的病例对照分析，共2,332例肺癌病例和2,457名对照的基于基因的关联分析表明，CD133是肺癌的易感基因(P 0.043)，CD133 3非翻译区的SNP rs2240688A和GT；C是与肺癌风险最显著的关联(P 0.020)；进一步的分析表明，rs2240688C变异基因型(CACC)具有降低肺癌风险的作用(优势比0.80；肺癌患者的中位生存期(中位生存期：15个月)优于AA(中位生存期：11个月，对数等级检验：P3.31 10(6)；COX模型：危险比0.81，95%CI 0.700.94)。功能分析表明，rs2240688A向rs2240688C的转变获得了新的microRNA hsa-miR-135a/b结合，并降低了CD133的表达。我们的数据表明，CD133的功能多态rs2240688A和gt；C与肺癌风险和生存期有关。该SNP可能是预测肺癌风险和预后的功能性生物标志物。
CD133 is a pivotal marker of cancer stem cells (CSCs), which is involved in tumorigenesis and cancer progression. Recent studies have identified CD133 to be a prognostic factor for cancer rested with its expression and genetic variants. Here, we hypothesized that the single nuclear polymorphisms (SNPs) in CD133 may be associated with lung cancer risk and prognosis. Based on three independent casecontrol analyses with a total of 2332 lung cancer cases and 2457 controls, the gene-based association analysis with 13 polymorphisms of CD133 suggested that CD133 is a susceptible gene for lung cancer (P 0.043) and that the SNP rs2240688A > C in the 3-untranslated region of CD133 is the most significant associated SNP with the risk of lung cancer (P 0.020); further analysis showed that the rs2240688C variant genotypes (CACC) harbored a decreased risk of lung cancer (odds ratio 0.80; 95% confidence interval (CI) 0.720.90) and conferred a favorable survival for lung cancer patients (median survival time: 15 months) compared with AA genotype (median survival time: 11 months, log-rank test: P 3.31 10(6); Cox model: hazards ratio 0.81, 95% CI 0.700.94). Functional assays revealed that the rs2240688A to rs2240688C transition gained a new binding of the microRNA hsa-miR-135a/b and decreased the CD133 expression. Our data suggest that the functional polymorphism rs2240688A > C in CD133 is associated with lung cancer risk and survival. This SNP may be a functional biomarker to predict risk and prognosis of lung cancer.