Department of Obstetrics and Gynaecology, University of Würzburg, School of Medicine, Josef-Schneider-Strasse 4, Würzburg 97080, Germany.
Br J Cancer. 2010 Aug 24;103(5):693-700. doi: 10.1038/sj.bjc.6605833. Epub 2010 Aug 3.
Screening is an unsolved problem for ovarian cancer (OvCA). As late detection is equivalent to poor prognosis, we analysed whether OvCA patients show diagnostically meaningful microRNA (miRNA) patterns in blood cells.
Blood-borne whole miRNome profiles from 24 patients with OvCA and 15 age- and sex-matched healthy controls were biostatistically evaluated.
Student's t-test revealed 147 significantly deregulated miRNAs before and 4 after Benjamini-Hochberg adjustment. Although these included miRNAs already linked to OvCA (e.g., miR-16, miR-155), others had never before been connected to specific diseases. A bioinformatically calculated miRNA profile allowed for discrimination between blood samples of OvCA patients and healthy controls with an accuracy of >76%. When only cancers of the serous subtype were considered and compared with an extended control group (n=39), accuracy, specificity and sensitivity all increased to >85%.
Our proof-of-principle study strengthens the hypothesis that neoplastic diseases generate characteristic miRNA fingerprints in blood cells. Still, the obtained OvCA-associated miRNA pattern is not yet sensitive and specific enough to permit the monitoring of disease progression or even preventive screening. Microarray-based miRNA profiling from peripheral blood could thus be combined with other markers to improve the notoriously difficult but important screening for OvCA.
卵巢癌(OvCA)的筛查仍是一个悬而未决的问题。由于晚期发现等同于预后不良,我们分析了卵巢癌患者的血细胞中是否存在具有诊断意义的微小 RNA(miRNA)模式。
对 24 例卵巢癌患者和 15 例年龄和性别匹配的健康对照者的血液全 miRNA 组进行了生物统计学评估。
学生 t 检验显示,在 Benjamini-Hochberg 调整前有 147 个 miRNA 明显下调,调整后有 4 个 miRNA 下调。虽然其中包括已经与 OvCA 相关的 miRNA(如 miR-16、miR-155),但其他 miRNA 以前从未与特定疾病相关联。通过计算 miRNA 谱,可以将卵巢癌患者和健康对照者的血液样本以 >76%的准确率区分开来。当仅考虑浆液性亚型的癌症并与扩展对照组(n=39)进行比较时,准确率、特异性和敏感性均提高到 >85%。
我们的初步研究结果支持这样一种假设,即肿瘤疾病会在血细胞中产生特征性的 miRNA 指纹。然而,所获得的与 OvCA 相关的 miRNA 模式还不够敏感和特异,无法监测疾病进展,甚至无法进行预防性筛查。因此,基于微阵列的外周血 miRNA 分析可以与其他标志物相结合,以改善对卵巢癌这一公认困难但重要的筛查。