Genome-wide maps of circulating miRNA biomarkers for ulcerative colitis.
Genome-wide maps of circulating miRNA biomarkers for ulcerative colitis.
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DOI：
10.1371/journal.pone.0031241
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Jones KW
中科院分区：
文献类型：
--
作者：
Duttagupta R;DiRienzo S;Jiang R;Bowers J;Gollub J;Kao J;Kearney K;Rudolph D;Dawany NB;Showe MK;Stamato T;Getts RC;Jones KW
炎症性肠病-包括克罗恩病和溃疡性结肠炎（UC）-是一种复杂的，多因素的胃肠道炎症性疾病。在这项研究中，我们探索了自然存在的循环miRNA作为潜在的血液生物标志物的效用，用于非侵入性预测UC发病率。从20名UC患者和20名正常个体的队列中构建了微泡、外周血单核细胞和血小板中循环miRNA的全基因组图谱。通过微阵列的显著性分析，已经鉴定了31种差异表达的血小板衍生的miRNA的特征，并且通过使用支持向量机的非概率二元线性分类来估计生物标志物性能。通过这种方法，分类器测量揭示了在区分UC患者与正常个体方面的92.8%准确性、96.2%特异性和89.5%灵敏度的预测评分。此外，血小板来源的生物标志物特征可以通过qPCR测定以88%的准确度验证，并且可以证明该组中的大多数miRNA亚分层为4个高度相关的基于强度的簇。对这些生物标志物的预测靶点的分析揭示了与细胞骨架组装、转运、膜通透性和参与各种调节级联的转录因子的调节相关的途径的富集，这些调节级联与肠道炎症的细胞介导的免疫应答模型一致。有趣的是，通过全基因组关联研究比较miRNA生物标志物组和IBD中涉及的遗传基因座，确定了hsa-miR-941与位于Chr 20上的UC易感基因座之间的物理联系。总之，对这些表达图谱的分析概述了具有临床实用性的新型血小板源性miRNA生物标志物的有希望的目录，并提供了对这些候选物在疾病发病机制中的潜在生物学功能的深入了解。
Inflammatory Bowel Disease – comprised of Crohn's Disease and Ulcerative Colitis (UC) - is a complex, multi-factorial inflammatory disorder of the gastrointestinal tract. In this study we have explored the utility of naturally occurring circulating miRNAs as potential blood-based biomarkers for non-invasive prediction of UC incidences. Whole genome maps of circulating miRNAs in micro-vesicles, Peripheral Blood Mononuclear Cells and platelets have been constructed from a cohort of 20 UC patients and 20 normal individuals. Through Significance Analysis of Microarrays, a signature of 31 differentially expressed platelet-derived miRNAs has been identified and biomarker performance estimated through a non-probabilistic binary linear classification using Support Vector Machines. Through this approach, classifier measurements reveal a predictive score of 92.8% accuracy, 96.2% specificity and 89.5% sensitivity in distinguishing UC patients from normal individuals. Additionally, the platelet-derived biomarker signature can be validated at 88% accuracy through qPCR assays, and a majority of the miRNAs in this panel can be demonstrated to sub-stratify into 4 highly correlated intensity based clusters. Analysis of predicted targets of these biomarkers reveal an enrichment of pathways associated with cytoskeleton assembly, transport, membrane permeability and regulation of transcription factors engaged in a variety of regulatory cascades that are consistent with a cell-mediated immune response model of intestinal inflammation. Interestingly, comparison of the miRNA biomarker panel and genetic loci implicated in IBD through genome-wide association studies identifies a physical linkage between hsa-miR-941 and a UC susceptibility loci located on Chr 20. Taken together, analysis of these expression maps outlines a promising catalog of novel platelet-derived miRNA biomarkers of clinical utility and provides insight into the potential biological function of these candidates in disease pathogenesis.
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影响因子：
14.9
作者：
Griffiths-Jones, S
通讯作者：
Griffiths-Jones, S
影响因子：
2.5
作者：
Borel, Christelle;Antonarakis, Stylianos E.
通讯作者：
Antonarakis, Stylianos E.
影响因子：
3.7
作者：
Hunter, Melissa Piper;Ismail, Noura;Zhang, Xiaoli;Aguda, Baltazar D.;Lee, Eun Joo;Yu, Lianbo;Xiao, Tao;Schafer, Jeffrey;Lee, Mei-Ling Ting;Schmittgen, Thomas D.;Nana-Sinkam, S. Patrick;Jarjoura, David;Marsh, Clay B.
通讯作者：
Marsh, Clay B.
影响因子：
9.8
作者：
John B;Enright AJ;Aravin A;Tuschl T;Sander C;Marks DS
通讯作者：
Marks DS
影响因子：
7.5
作者：
CORTES, C;VAPNIK, V
通讯作者：
VAPNIK, V