Associations between cuprotosis-related genes and the spectrum of metabolic dysfunction-associated fatty liver disease: An exploratory study.
Autor: | Yuan HY; MAFLD Research Center, Department of Hepatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China., Liu WY; Department of Endocrinology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China., Feng G; Xi'an Medical University, Xi'an, China., Chen SD; Department of Pathology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China., Jin XZ; Department of Laboratory Medicine, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China., Chen LL; MAFLD Research Center, Department of Hepatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China., Song ZJ; The First Affiliated Hospital, School of Public Health, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China., Li K; School of Biomedical Engineering, School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, China., Byrne CD; Southampton National Institute for Health and Care Research Biomedical Research Centre, University Hospital Southampton and University of Southampton, Southampton General Hospital, Southampton, UK., Targher G; Metabolic Diseases Research Unit, IRCCS Sacro Cuore-Don Calabria Hospital, Negrar di Valpolicella, Italy., Tian N; MAFLD Research Center, Department of Hepatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China., Li G; Department of Infectious, Jining No.1 People's Hospital, Jining, China., Zhang XL; MAFLD Research Center, Department of Hepatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China., George J; Storr Liver Centre, Westmead Hospital and University of Sydney, Westmead, Australia., Zhou M; School of Biomedical Engineering, School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, China., Wang F; The First Affiliated Hospital, School of Public Health, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China., Zheng MH; MAFLD Research Center, Department of Hepatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.; Institute of Hepatology, Wenzhou Medical University, Wenzhou, China.; Key Laboratory of Diagnosis and Treatment for The Development of Chronic Liver Disease in Zhejiang Province, Wenzhou, China. |
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Jazyk: | angličtina |
Zdroj: | Diabetes, obesity & metabolism [Diabetes Obes Metab] 2024 Dec; Vol. 26 (12), pp. 5757-5775. Date of Electronic Publication: 2024 Sep 16. |
DOI: | 10.1111/dom.15946 |
Abstrakt: | Aims: To explore the associations between cuprotosis-related genes (CRGs) across different stages of liver disease in metabolic dysfunction-associated fatty liver disease (MAFLD), including hepatocellular carcinoma (HCC). Materials and Methods: We analysed several bulk RNA sequencing datasets from patients with MAFLD (n = 331) and MAFLD-related HCC (n = 271) and two MAFLD single-cell RNA sequencing datasets. To investigate the associations between CRGs and MAFLD, we performed differential correlation, logistic regression and functional enrichment analyses. We also validated the findings in an independent Wenzhou PERSONS cohort of MAFLD patients (n = 656) used for a genome-wide association study (GWAS). Results: GLS, GCSH and ATP7B genes showed significant differences across the MAFLD spectrum and were significantly associated with liver fibrosis stages. GLS was closely associated with fibrosis stages in patients with MAFLD and those with MAFLD-related HCC. GLS is predominantly expressed in monocytes and T cells in MAFLD. During the progression of metabolic dysfunction-associated fatty liver to metabolic-associated steatohepatitis, GLS expression in T cells decreased. GWAS revealed that multiple single nucleotide polymorphisms in GLS were associated with clinical indicators of MAFLD. Conclusions: GLS may contribute to liver inflammation and fibrosis in MAFLD mainly through cuprotosis and T-cell activation, promoting the progression of MAFLD to HCC. These findings suggest that cuprotosis may play a role in MAFLD progression, potentially providing new insights into MAFLD pathogenesis. (© 2024 John Wiley & Sons Ltd.) |
Databáze: | MEDLINE |
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