Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Magdeburg, Germany.
Gastroenterology Division, First Department of Internal Medicine, Semmelweis University, Budapest, Hungary.
Inflamm Bowel Dis. 2018 Jun 8;24(7):1547-1557. doi: 10.1093/ibd/izy046.
Assessment of the disease activity in inflammatory bowel disease (IBD) is essential for adequate treatment management and reliable noninvasive biomarkers for verification of mucosal healing are still needed. MicroRNAs (miRNAs) are differentially expressed in IBD and cancer. We aimed to evaluate the potential of circulating and fecal miRNAs as diagnostic biomarkers for IBD.
In this proof-of-principle study we used 2 independent patient cohorts. Testing cohort (n = 96) included serum and fecal samples from controls (n = 35) and IBD patients (n = 61) including 43 patients with Crohn's disease (CD), 18 with ulcerative colitis (UC) with an active disease (n = 38), or in remission (n = 23). Validation cohort included fecal samples from patients with calprotectin/endoscopy-confirmed active disease (n = 30) or in remission (n = 15). Target-based approach (miR-16, miR-21, miR-155, and miR-223) has been used to evaluate miRNA expression.
Sera samples from IBD patients showed higher level of miR-16, miR-21, and miR-223, but not miR-155, compared to controls and was higher in CD than in UC patients. Much stronger miRNA expression changes were observed in feces from IBD patients for all studied miRNAs with highest expression of miR-155 and miR-223 in testing and validation cohorts. MiRNA expression correlated with clinical remission, however, only fecal but not circulating miRNAs, correlated with surrogate parameters such as fecal calprotectin or C-reactive protein.
Our data provide a novel evidence for differential expression level of fecal miRNAs in IBD. We demonstrate that miRNAs in feces correlate with disease activity and may be considered as potential tool for the further biomarker research in IBD. 10.1093/ibd/izy046_video1izy046.video15794822319001.
评估炎症性肠病（IBD）的疾病活动度对于进行充分的治疗管理至关重要，仍需要可靠的非侵入性生物标志物来验证黏膜愈合。microRNAs（miRNAs）在 IBD 和癌症中表达不同。我们旨在评估循环和粪便 miRNAs 作为 IBD 诊断生物标志物的潜力。
在这项原理验证研究中，我们使用了 2 个独立的患者队列。检测队列（n=96）包括来自对照者（n=35）和 IBD 患者（n=61）的血清和粪便样本，其中包括 43 例克罗恩病（CD）患者、18 例活动期（n=38）或缓解期（n=23）溃疡性结肠炎（UC）患者。验证队列包括粪便样本，这些样本来自粪便钙卫蛋白/内镜确诊的活动期（n=30）或缓解期（n=15）患者。采用基于靶标的方法（miR-16、miR-21、miR-155 和 miR-223）来评估 miRNA 的表达。
与对照者相比，IBD 患者的血清样本显示 miR-16、miR-21 和 miR-223 水平升高，而 miR-155 水平没有升高，并且 CD 患者的水平高于 UC 患者。在所有研究的 miRNA 中，IBD 患者粪便中的 miRNA 表达变化更为明显，在检测和验证队列中，miR-155 和 miR-223 的表达最高。miRNA 表达与临床缓解相关，但只有粪便而非循环 miRNA 与粪便钙卫蛋白或 C 反应蛋白等替代参数相关。
我们的数据为 IBD 中粪便 miRNAs 的差异表达水平提供了新的证据。我们证明粪便中的 miRNAs 与疾病活动度相关，可作为 IBD 进一步生物标志物研究的潜在工具。
