Division of Gastroenterology and Nutrition, Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
J Pediatr Gastroenterol Nutr. 2011 Jul;53(1):26-33. doi: 10.1097/MPG.0b013e31822200cc.
The gold standard for the diagnosis and evaluation of Crohn disease (CD) is endoscopy/colonoscopy, although this is invasive, costly, and associated with risks to the patient. Recently, circulating microRNAs (miRNAs) have emerged as promising noninvasive biomarkers. Here, we examined the utility of serum miRNAs as biomarkers of CD in children.
Studies were conducted using sera samples from patients with pediatric CD, healthy controls, and a comparison group of patients with pediatric celiac disease. Serum miRNA levels were explored initially using a microfluidic quantitative reverse transcription-polymerase chain reaction array platform. Findings were subsequently validated using quantitative reverse transcription-polymerase chain reaction in larger validation sample sets. The diagnostic utility of CD-associated serum miRNA was examined using receiver operating characteristic analysis.
A survey of miRNA levels in the sera of control and patients with CD detected significant elevation of 24 miRNAs, 11 of which were chosen for further validation. All of the candidate biomarker miRNAs were confirmed in an independent CD sample set (n = 46). To explore the specificity of the CD-associated miRNAs, they were measured in the sera of patients with celiac disease (n = 12); none were changed compared with healthy controls. Receiver operating characteristic analyses revealed that serum miRNAs have promising diagnostic utility, with sensitivities for CD above 80%. Significant decreases in serum miRNAs were observed in 24 incident patients with pediatric CD after 6 months of treatment.
The present study identifies 11 CD-associated serum miRNA with encouraging diagnostic potential. Our findings suggest serum miRNAs may prove useful as noninvasive biomarkers in CD.
克罗恩病（CD）的诊断和评估的金标准是内镜/结肠镜检查，尽管这是侵入性的，昂贵的，并与患者的风险。最近，循环microRNAs（miRNAs）已经成为有前途的非侵入性生物标志物。在这里，我们研究了血清miRNAs作为儿童 CD 的生物标志物的效用。
使用来自儿科 CD 患者、健康对照者和儿科乳糜泻患者比较组的血清样本进行了研究。最初使用微流控定量逆转录聚合酶链反应阵列平台探索血清 miRNA 水平。使用定量逆转录聚合酶链反应在更大的验证样本集中进一步验证发现。使用受试者工作特征分析检查与 CD 相关的血清 miRNA 的诊断效用。
对对照和 CD 患者血清中 miRNA 水平的调查发现，24 种 miRNA 显著升高，其中 11 种 miRNA 被选择用于进一步验证。所有候选生物标志物 miRNA 均在独立的 CD 样本组（n=46）中得到确认。为了探索与 CD 相关的 miRNA 的特异性，在乳糜泻患者（n=12）的血清中测量了它们；与健康对照组相比，没有任何变化。受试者工作特征分析显示，血清 miRNA 具有有前途的诊断效用，其 CD 敏感性超过 80%。在接受治疗的 24 例儿科 CD 新发病例中，观察到血清 miRNA 显著降低。
本研究确定了 11 种与 CD 相关的血清 miRNA，具有令人鼓舞的诊断潜力。我们的研究结果表明，血清 miRNA 可能是 CD 非侵入性生物标志物的有用工具。
