微小RNA可对克罗恩病的不同疾病行为表型进行分类，且可能具有预后价值。
MicroRNAs Classify Different Disease Behavior Phenotypes of Crohn's Disease and May Have Prognostic Utility.
作者信息
Peck Bailey C E, Weiser Matthew, Lee Saangyoung E, Gipson Gregory R, Iyer Vishal B, Sartor Ryan B, Herfarth Hans H, Long Millie D, Hansen Jonathan J, Isaacs Kim L, Trembath Dimitri G, Rahbar Reza, Sadiq Timothy S, Furey Terrence S, Sethupathy Praveen, Sheikh Shehzad Z
机构信息
*Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; †Department of Medicine, Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; ‡Department of Medicine, Curriculum in Bioinformatics and Computational Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; §Department of Medicine, Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Departments of ||Pathology and ¶Surgery, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; **Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; and ††Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
出版信息
Inflamm Bowel Dis. 2015 Sep;21(9):2178-87. doi: 10.1097/MIB.0000000000000478.
BACKGROUND
There is a dire need for reliable prognostic markers that can guide effective therapeutic intervention in Crohn's disease (CD). We examined whether different phenotypes in CD can be classified based on colonic microRNA (miRNA) expression and whether miRNAs have prognostic utility for CD.
METHODS
High-throughput sequencing of small and total RNA isolated from colon tissue from patients with CD and controls without Inflammatory Bowel Disease (non-IBD) was performed. To identify miRNAs associated with specific phenotypes of CD, patients were stratified according to disease behavior (nonstricturing, nonpenetrating; stricturing; penetrating), and miRNA profiles in each subset were compared with those of the non-IBD group. Validation assays were performed using quantitative reverse transcription polymerase chain reaction. These miRNAs were further evaluated by quantitative reverse transcriptase polymerase chain reaction on formalin-fixed, paraffin-embedded tissue (index biopsies) of patients with nonpenetrating CD at the time of diagnosis that either retained the nonpenetrating phenotype or progressed to penetrating/fistulizing CD.
RESULTS
We found a suite of miRNAs, including miR-31-5p, miR-215, miR-223-3p, miR-196b-5p, and miR-203 that stratify patients with CD according to disease behavior independent of the effect of inflammation. Furthermore, we also demonstrated that expression levels of miR-215 in index biopsies of patients with CD might predict the likelihood of progression to penetrating/fistulizing CD. Finally, using a novel statistical simulation approach applied to colonic RNA-sequencing data for patients with CD and non-IBD controls, we identified miR-31-5p and miR-203 as candidate master regulators of gene expression profiles associated with CD.
CONCLUSIONS
miRNAs may serve as clinically useful prognostic markers guiding initial therapy and identifying patients who would benefit most from effective intervention.
背景
迫切需要可靠的预后标志物来指导克罗恩病（CD）的有效治疗干预。我们研究了是否可以根据结肠微小RNA（miRNA）表达对CD的不同表型进行分类，以及miRNA对CD是否具有预后效用。
方法
对来自CD患者和无炎症性肠病（非IBD）对照的结肠组织中分离的小RNA和总RNA进行高通量测序。为了鉴定与CD特定表型相关的miRNA，根据疾病行为（非狭窄、非穿透性；狭窄；穿透性）对患者进行分层，并将每个亚组中的miRNA谱与非IBD组进行比较。使用定量逆转录聚合酶链反应进行验证试验。在诊断时对非穿透性CD患者的福尔马林固定、石蜡包埋组织（索引活检）进行定量逆转录酶聚合酶链反应，进一步评估这些miRNA，这些患者要么保持非穿透性表型，要么进展为穿透性/瘘管性CD。
结果
我们发现了一组miRNA，包括miR-31-5p、miR-215、miR-223-3p、miR-196b-5p和miR-203，它们可根据疾病行为对CD患者进行分层，而不受炎症影响。此外，我们还证明，CD患者索引活检中miR-215的表达水平可能预测进展为穿透性/瘘管性CD的可能性。最后，使用一种应用于CD患者和非IBD对照的结肠RNA测序数据的新型统计模拟方法，我们确定miR-31-5p和miR-203是与CD相关的基因表达谱的候选主调节因子。
结论
miRNA可作为临床有用的预后标志物，指导初始治疗并识别最能从有效干预中获益的患者。
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