Keller Andreas, Leidinger Petra, Vogel Britta, Backes Christina, ElSharawy Abdou, Galata Valentina, Mueller Sabine C, Marquart Sabine, Schrauder Michael G, Strick Reiner, Bauer Andrea, Wischhusen Jörg, Beier Markus, Kohlhaas Jochen, Katus Hugo A, Hoheisel Jörg, Franke Andre, Meder Benjamin, Meese Eckart
Chair for Clinical Bioinformatics, Saarland University, Saarbrücken, Germany.
Institute of Human Genetics, Saarland University, Homburg, Germany.
BMC Med. 2014 Dec 3;12:224. doi: 10.1186/s12916-014-0224-0.
miRNA profiles are promising biomarker candidates for a manifold of human pathologies, opening new avenues for diagnosis and prognosis. Beyond studies that describe miRNAs frequently as markers for specific traits, we asked whether a general pattern for miRNAs across many diseases exists.
We evaluated genome-wide circulating profiles of 1,049 patients suffering from 19 different cancer and non-cancer diseases as well as unaffected controls. The results were validated on 319 individuals using qRT-PCR.
We discovered 34 miRNAs with strong disease association. Among those, we found substantially decreased levels of hsa-miR-144* and hsa-miR-20b with AUC of 0.751 (95% CI: 0.703-0.799), respectively. We also discovered a set of miRNAs, including hsa-miR-155*, as rather stable markers, offering reasonable control miRNAs for future studies. The strong downregulation of hsa-miR-144* and the less variable pattern of hsa-miR-155* has been validated in a cohort of 319 samples in three different centers. Here, breast cancer as an additional disease phenotype not included in the screening phase has been included as the 20th trait.
Our study on 1,368 patients including 1,049 genome-wide miRNA profiles and 319 qRT-PCR validations further underscores the high potential of specific blood-borne miRNA patterns as molecular biomarkers. Importantly, we highlight 34 miRNAs that are generally dysregulated in human pathologies. Although these markers are not specific to certain diseases they may add to the diagnosis in combination with other markers, building a specific signature. Besides these dysregulated miRNAs, we propose a set of constant miRNAs that may be used as control markers.
微小RNA（miRNA）谱有望成为多种人类疾病的生物标志物候选物，为诊断和预后开辟了新途径。除了那些经常将miRNA描述为特定特征标志物的研究外，我们还探讨了是否存在多种疾病中miRNA的通用模式。
我们评估了1049名患有19种不同癌症和非癌症疾病的患者以及未受影响对照的全基因组循环miRNA谱。结果在319名个体中使用定量逆转录聚合酶链反应（qRT-PCR）进行了验证。
我们发现了34种与疾病有强关联的miRNA。其中，我们发现hsa-miR-144和hsa-miR-20b水平大幅降低，曲线下面积（AUC）分别为0.751（95%置信区间：0.703-0.799）。我们还发现了一组miRNA，包括hsa-miR-155，它们是相当稳定的标志物，可为未来研究提供合理的对照miRNA。hsa-miR-144的强烈下调和hsa-miR-155的较少变化模式在三个不同中心的319个样本队列中得到了验证。在这里，乳腺癌作为筛查阶段未包括的另一种疾病表型被纳入作为第20种特征。
我们对1368名患者的研究，包括1049个全基因组miRNA谱和319次qRT-PCR验证，进一步强调了特定血源性miRNA模式作为分子生物标志物的高潜力。重要的是，我们突出了34种在人类疾病中普遍失调的miRNA。尽管这些标志物并非特定于某些疾病，但它们可能与其他标志物结合用于诊断，构建特定的特征。除了这些失调的miRNA外，我们还提出了一组可作为对照标志物的恒定miRNA。
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