Mathematical Models Including microRNA Levels of Mesenteric Adipose Tissue May Predict Postoperative Relapse in Crohn’s Disease Patients

Karine Mariane Steigleder; Lívia Bitencourt Pascoal; Natália Souza Nunes Siqueira; Laís Angélica de Paula Simino; Maria de Lourdes Setsuko Ayrizono; Marciane Milanski Ferreira; João José Fagundes; Aníbal Tavares de Azevedo; Adriana Souza Torsoni; Raquel Franco Leal

Gastro Hep Advances (Jan 2024)

Mathematical Models Including microRNA Levels of Mesenteric Adipose Tissue May Predict Postoperative Relapse in Crohn’s Disease Patients

Karine Mariane Steigleder,
Lívia Bitencourt Pascoal,
Natália Souza Nunes Siqueira,
Laís Angélica de Paula Simino,
Maria de Lourdes Setsuko Ayrizono,
Marciane Milanski Ferreira,
João José Fagundes,
Aníbal Tavares de Azevedo,
Adriana Souza Torsoni,
Raquel Franco Leal

Affiliations

Karine Mariane Steigleder: Inflammatory Bowel Diseases Research Laboratory, Gastrocenter, Colorectal Surgery Unit, Surgery Department, School of Medical Sciences, University of Campinas (Unicamp), Campinas, São Paulo, Brazil
Lívia Bitencourt Pascoal: Inflammatory Bowel Diseases Research Laboratory, Gastrocenter, Colorectal Surgery Unit, Surgery Department, School of Medical Sciences, University of Campinas (Unicamp), Campinas, São Paulo, Brazil
Natália Souza Nunes Siqueira: Inflammatory Bowel Diseases Research Laboratory, Gastrocenter, Colorectal Surgery Unit, Surgery Department, School of Medical Sciences, University of Campinas (Unicamp), Campinas, São Paulo, Brazil
Laís Angélica de Paula Simino: Laboratory of Metabolic Disorders, School of Applied Sciences, University of Campinas (Unicamp), Limeira, São Paulo, Brazil
Maria de Lourdes Setsuko Ayrizono: Inflammatory Bowel Diseases Research Laboratory, Gastrocenter, Colorectal Surgery Unit, Surgery Department, School of Medical Sciences, University of Campinas (Unicamp), Campinas, São Paulo, Brazil
Marciane Milanski Ferreira: Laboratory of Metabolic Disorders, School of Applied Sciences, University of Campinas (Unicamp), Limeira, São Paulo, Brazil
João José Fagundes: Inflammatory Bowel Diseases Research Laboratory, Gastrocenter, Colorectal Surgery Unit, Surgery Department, School of Medical Sciences, University of Campinas (Unicamp), Campinas, São Paulo, Brazil
Aníbal Tavares de Azevedo: Simulation Laboratory, School of Applied Sciences, University of Campinas (Unicamp), Limeira, Brazil
Adriana Souza Torsoni: Laboratory of Metabolic Disorders, School of Applied Sciences, University of Campinas (Unicamp), Limeira, São Paulo, Brazil
Raquel Franco Leal: Inflammatory Bowel Diseases Research Laboratory, Gastrocenter, Colorectal Surgery Unit, Surgery Department, School of Medical Sciences, University of Campinas (Unicamp), Campinas, São Paulo, Brazil; Correspondence: Address correspondence to: Raquel Franco Leal, MD, PhD, IBD Research Laboratory, Gastrocenter, Colorectal Surgery Unit, Surgery Department, Carlos Chagas Street, 420, Cidade Universitária Zeferino Vaz, 13083-878, Campinas, São Paulo, Brazil.

Journal volume & issue: Vol. 3, no. 1
pp. 17 – 30

Abstract

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Background and Aims: 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. Methods: 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 (P value .99; correct predictions of more than 60%). Results: miRNA-650 and miRNA-29c were upregulated in the MAT of CD compared to the control group (P < .0001 and P = .0032, respectively), besides presenting decreased levels of their target genes. Two were target genes of the miRNA-650: glutamine-fructose-6-phosphate transaminase 2 (P = .012) and aldehyde dehydrogenase 4 family (P = .0035); and 4 were targets of the miRNA-29c: cell death-inducing DFFA-like effector c (P = .001), E2F transcription factor-1 (P = .007), hypoxia-inducible factor 3 subunit alpha (P = .0029), and pyruvate dehydrogenase kinase 4 (P = .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. Conclusion: 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.

Published in Gastro Hep Advances

ISSN: 2772-5723 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Diseases of the digestive system. Gastroenterology
Website: https://www.sciencedirect.com/journal/gastro-hep-advances

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