A microRNA expression signature for cervical cancer prognosis.

A microRNA expression signature for cervical cancer prognosis.
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宫颈癌预后的 microRNA 表达特征。

DOI:
10.1158/0008-5472.can-09-3289
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发表时间:
2010-02-15
期刊:
影响因子:
11.2
通讯作者:
Wang X
Wang X
中科院分区:
医学1区
文献类型:
--
作者:
Hu X;Schwarz JK;Lewis JS Jr;Huettner PC;Rader JS;Deasy JO;Grigsby PW;Wang X

文献摘要

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浸润性宫颈癌是全球女性癌症死亡的主要原因,每年导致约30万人死亡。宫颈癌的临床结局差异很大,难以预测。因此,通过在治疗前识别具有治疗失败高风险的患者,可靠地预测疾病结果的方法对于个体化治疗将是重要的。在这项研究中,我们已经确定了一个基于microRNA的签名,用于预测宫颈癌的生存率。microRNAs(miRNAs)是近年来发现的一类与人类肿瘤密切相关的小分子非编码RNA。使用我们最近建立的基于PCR的miRNA检测,我们分析了102例宫颈癌,并鉴定了两种可能预测患者生存的miRNA(miR-200 a和miR-9)。基于这两种miRNAs开发了逻辑回归模型,随后用42例独立的宫颈癌验证了该模型的预后价值。此外,进行功能研究以表征miRNA在宫颈癌细胞中的作用。我们的研究结果表明,miR-200 a和miR-9在宫颈癌控制中可能发挥重要的调控作用。特别是,miR-200 a可能通过同时抑制对细胞运动性重要的多个基因的表达来影响宫颈癌细胞的转移潜力。
Invasive cervical cancer is a leading cause of cancer death in women worldwide, resulting in about 300,000 deaths each year. The clinical outcomes of cervical cancer vary significantly and are difficult to predict. Thus, a method to reliably predict disease outcome would be important for individualized therapy by identifying patients with high-risk of treatment failures prior to therapy. In this study, we have identified a microRNA-based signature for the prediction of cervical cancer survival. MicroRNAs (miRNAs) are a newly identified family of small non-coding RNAs that are extensively involved in human cancers. Using our recently established PCR-based miRNA assays, we have analyzed 102 cervical cancers and identified two miRNAs (miR-200a and miR-9) that are likely to predict patient survival. A logistic regression model was developed based on these two miRNAs and the prognostic value of the model was subsequently validated with 42 independent cervical cancers. Furthermore, functional studies were performed to characterize the effect of miRNAs in cervical cancer cells. Our results suggest that both miR-200a and miR-9 could play important regulatory roles in cervical cancer control. In particular, miR-200a is likely to affect the metastatic potential of cervical cancer cells by simultaneously suppressing the expression of multiple genes that are important to cell motility.