Departments of Radiation Oncology, Pathology and Immunology, and Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Cancer Res. 2010 Feb 15;70(4):1441-8. doi: 10.1158/0008-5472.CAN-09-3289. Epub 2010 Feb 2.
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 before therapy. In this study, we have identified a microRNA (miRNA)-based signature for the prediction of cervical cancer survival. miRNAs are a newly identified family of small noncoding RNAs that are extensively involved in human cancers. Using an established PCR-based miRNA assay to analyze 102 cervical cancer samples, we identified miR-200a and miR-9 as two miRNAs that could 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 independent cervical cancers. Furthermore, functional studies were done 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 coordinate suppression of multiple genes controlling cell motility.
浸润性宫颈癌是全世界女性癌症死亡的主要原因，每年导致约 30 万人死亡。宫颈癌的临床结果差异很大，难以预测。因此，一种可靠的预测疾病结果的方法对于通过在治疗前识别出治疗失败风险高的患者来进行个体化治疗非常重要。在这项研究中，我们已经确定了一个基于 microRNA (miRNA) 的signature 来预测宫颈癌的生存。miRNAs 是一类新发现的小型非编码 RNA，广泛参与人类癌症。我们使用已建立的基于 PCR 的 miRNA 检测方法分析了 102 个宫颈癌样本，发现 miR-200a 和 miR-9 是两种可以预测患者生存的 miRNA。基于这两个 miRNA 建立了一个逻辑回归模型，并随后使用独立的宫颈癌样本验证了该模型的预后价值。此外，还进行了功能研究以表征 miRNA 在宫颈癌细胞中的作用。我们的结果表明，miR-200a 和 miR-9 都可能在宫颈癌的控制中发挥重要的调节作用。特别是，miR-200a 可能通过协调抑制多个控制细胞运动的基因来影响宫颈癌细胞的转移潜力。
