Steigleder Karine Mariane, Pascoal Lívia Bitencourt, Siqueira Natália Souza Nunes, Simino Laís Angélica de Paula, Ayrizono Maria de Lourdes Setsuko, Ferreira Marciane Milanski, Fagundes João José, Azevedo Aníbal Tavares de, Torsoni Adriana Souza, Leal Raquel Franco
Inflammatory Bowel Diseases Research Laboratory, Gastrocenter, Colorectal Surgery Unit, Surgery Department, School of Medical Sciences, University of Campinas (Unicamp), Campinas, São Paulo, Brazil.
Laboratory of Metabolic Disorders, School of Applied Sciences, University of Campinas (Unicamp), Limeira, São Paulo, Brazil.
Gastro Hep Adv. 2023 Sep 14;3(1):17-30. doi: 10.1016/j.gastha.2023.08.020. eCollection 2024.
Recent evidence suggests that the mesenteric adipose tissue (MAT) near the affected intestine may play a role in Crohn's disease (CD) pathophysiology. Modulation of several transcripts has already been identified in the MAT of CD in the literature. Therefore, our aim was to validate the microRNA (miRNA) transcript levels and their target genes in the MAT of active CD patients and correlate them with clinical and epidemiological data.
Samples from the MAT of surgical specimens from 25 active CD patients were obtained. The control group comprised fifteen patients who underwent surgery for other diseases, except inflammatory bowel diseases. Transcriptional levels of miRNA and their target genes were assessed by quantitative real-time polymerase chain reaction. The correlation between transcripts and clinical characteristics was obtained using multiple linear regression. The mathematical models (M) underwent a statistical filter to ensure robustness and reliability ( value < .05; adjusted R-squared (Rˆ2)> .99; correct predictions of more than 60%).
miRNA-650 and miRNA-29c were upregulated in the MAT of CD compared to the control group ( < .0001 and = .0032, respectively), besides presenting decreased levels of their target genes. Two were target genes of the miRNA-650: glutamine-fructose-6-phosphate transaminase 2 ( = .012) and aldehyde dehydrogenase 4 family ( = .0035); and 4 were targets of the miRNA-29c: cell death-inducing DFFA-like effector c ( = .001), E2F transcription factor-1 ( = .007), hypoxia-inducible factor 3 subunit alpha ( = .0029), and pyruvate dehydrogenase kinase 4 ( = .0054). We found 2 M with statistical strength and robustness. The performance test identified one model with 100% accuracy for predicting the month of recurrence and determining patients with less risk of early relapse after surgery.
We demonstrate that miRNA-650 and miRNA-29c and some of their target genes, besides clinical and epidemiological variables, may be useful in a model to predict when disease relapse may occur in CD patients who underwent surgery. These findings constitute a potential tool to guide postoperative clinical management.
最近的证据表明，病变肠道附近的肠系膜脂肪组织（MAT）可能在克罗恩病（CD）的病理生理学中发挥作用。文献中已在CD的MAT中鉴定出几种转录本的调节情况。因此，我们的目的是验证活动期CD患者MAT中的微小RNA（miRNA）转录水平及其靶基因，并将它们与临床和流行病学数据相关联。
获取了25例活动期CD患者手术标本的MAT样本。对照组包括15例因其他疾病（除炎症性肠病外）接受手术的患者。通过定量实时聚合酶链反应评估miRNA及其靶基因的转录水平。使用多元线性回归获得转录本与临床特征之间的相关性。数学模型（M）经过统计筛选以确保稳健性和可靠性（P值<0.05；调整后的决定系数（R²）>.99；正确预测率超过60%）。
与对照组相比，CD的MAT中miRNA-650和miRNA-29c上调（分别为P <.0001和P =.0032），此外其靶基因水平降低。miRNA-650有两个靶基因：谷氨酰胺-果糖-6-磷酸转氨酶2（P =.012）和醛脱氢酶4家族（P =.0035）；miRNA-29c有4个靶基因：细胞死亡诱导DFFA样效应因子c（P =.001）、E2F转录因子-1（P =.007）、缺氧诱导因子3亚基α（P =.0029）和丙酮酸脱氢酶激酶4（P =.0054）。我们发现了2个具有统计学强度和稳健性的M。性能测试确定了一个模型，其预测复发月份和确定术后早期复发风险较低患者的准确率为100%。
我们证明，除了临床和流行病学变量外，miRNA-650和miRNA-29c及其一些靶基因可能有助于建立一个模型，以预测接受手术的CD患者疾病复发的时间。这些发现构成了指导术后临床管理的潜在工具。
