Profile of plasma microRNAs as a potential biomarker of Wilson’s disease

• Published in: Journal of gastroenterology 2024-10, Vol.59 (10), p.921-931
• Main Authors: Sánchez-Monteagudo, Ana, Ripollés, Edna, Murillo, Oihana, Domènech, Sofia, Álvarez-Sauco, María, Girona, Eva, Sastre-Bataller, Isabel, Bono, Ariadna, García-Villarreal, Luis, Tugores, Antonio, García-García, Francisco, González-Aseguinolaza, Gloria, Berenguer, Marina, Espinós, Carmen
• Format: Article
• Language: English
• Subjects: Abdominal Surgery; Adolescent; Adult; Alanine transaminase; Alanine Transaminase - blood; Animals; Aspartate Aminotransferases - blood; Aspartate transaminase; Biliary Tract; Biomarkers; Biomarkers - blood; Case-Control Studies; Circulating MicroRNA - blood; Circulating MicroRNA - genetics; Cohort Studies; Colorectal Surgery; Copper-Transporting ATPases - genetics; Disease Models, Animal; Disease Progression; Female; gamma-Glutamyltransferase - blood; Gastroenterology; Hepatolenticular Degeneration - blood; Hepatolenticular Degeneration - diagnosis; Hepatolenticular Degeneration - genetics; Hepatology; Humans; Liver - metabolism; Liver - pathology; Liver diseases; Male; Medical treatment; Medicine; Medicine & Public Health; Mice; Mice, Knockout; MicroRNAs; MicroRNAs - blood; MicroRNAs - genetics; miRNA; Original Article―Liver; Original ―Liver, Pancreas, and Biliary Tract; Pancreas; Prognosis; Surgical Oncology; Wilson's disease; Young Adult; γ-Glutamyltransferase
• ISSN: 0944-1174; 1435-5922; 1435-5922
• DOI: 10.1007/s00535-024-02135-6

Background Wilson’s disease (WD) is a rare condition resulting from autosomal recessive mutations in ATP7B , a copper transporter, manifesting with hepatic, neurological, and psychiatric symptoms. Timely diagnosis and appropriate treatment yield a positive prognosis, while delayed identification and/or insufficient therapy lead to a poor outcome. Our aim was to establish a prognostic method for WD by characterising biomarkers based on circulating microRNAs. Methods We conducted investigations across three cohorts: discovery, validation (comprising unrelated patients), and follow-up (revisiting the discovery cohort 3 years later). All groups were compared to age- and gender-matched controls. Plasma microRNAs were analysed via RNA sequencing in the discovery cohort and subsequently validated using quantitative PCR in all three cohorts. To assess disease progression, we examined the microRNA profile in Atp7b −/− mice, analysing serum samples from 6 to 44 weeks of age and liver samples at three time points: 20, 30, and 40 weeks of age. Results In patients, elevated levels of the signature microRNAs (miR-122-5p, miR-192-5p, and miR-885-5p) correlated with serum activities of aspartate transaminase, alanine aminotransferase and gamma-glutamyl transferase. In Atp7b −/− mice, levels of miR-122-5p and miR-192-5p (miR-885-5p lacking a murine orthologue) increased from 12 weeks of age in serum, while exhibiting fluctuations in the liver, possibly attributable to hepatocyte regenerative capacity post-injury and the release of hepatic microRNAs into the bloodstream. Conclusions The upregulation of the signature miR-122-5p, miR-192-5p, and miR-885-5p in patients and their correlation with liver disease progression in WD mice support their potential as biomarkers of WD.