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• W3204652247 abstract "Background: In patients with NAFLD liver biopsy is the gold standard to detect NASH and stage liver fibrosis. We aimed to identify differentially expressed mRNAs and non-coding RNAs in serum samples of biopsy-diagnosed mild and severe NAFLD patients with respect to controls and to each other. Methods: We first performed a whole transcriptome analysis through microarray (n=12: 4 CTRL; 4 mild NAFLD: NAS≤4 F0; 4 severe NAFLD NAS≥5 F3), followed by validation of selected transcripts through qPCRs in 88 subjects: 63 NAFLD, 25 CTRL. A similar analysis was also performed on HepG2 exposed to Oleate:Palmitate or only Palmitate (cellular model of NAFL/NASH) at intracellular/extracellular levels. Transcript correlation with histological/clinical data was also analyzed. Findings: We identified several DE coding/non-coding RNAs in each group of the study cohort. We validated the up-regulation of UBE2V1, BNIP3L mRNAs, and TGFB2/TGFB2-OT1 coding/ lncRNA both in patients with NAS ≥5 (versus NAS ≤ 4) and in patients with Fibrosis stages= 3-4 (versus F= 0-2). HBA2 mRNA and RP11-128N14.5 lncRNA were up-regulated respectively only in F=3-4 or NAS ≥5 patients. Analyzed transcript deregulation was also reflected in NAFL/NASH in vitro models. UBE2V1, RP11-128N14.5, BNIP3L, and TGFB2/TGFB2-OT1 correlated with histological/biochemical data. Combinations of TGFB2/TGFB2-OT1 FIB-4 (AUC=0.891, p-value=0.000003) or TGFB2/TGFB2-OT1 Fibroscan (AUC=0.892, p-value=0.000002) improved the detection of F=3-4 with respect to F=0-2 fibrosis stages. Interpretation: We identified specific serum coding/non-coding RNA profiles in severe and mild NAFLD patients that possibly mirror molecular mechanisms underlying NAFLD progression towards NASH/fibrosis. TGFB2/TGFB2-OT1 detection improves FIB-4/Fibroscan diagnostic performance for advanced fibrosis discrimination. Funding: This study was funded by 2016/2018 Department Research Plan of University of Catania, Department of Clinical and Experimental Medicine (project #A) and by 2016/2018 Department Research Plan of University of Catania (2nd line of intervention). Declaration of Interest: The Authors do not have any conflict of interest to declare. Ethical Approval:  This study was conducted according to the Declaration of Helsinki and was approved by the ethics committee of the University Hospital of Palermo. Before the procedures a written informed consent was obtained from all patients participating in this study." @default.
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• W3204652247 date "2018-01-01" @default.
• W3204652247 modified "2023-09-25" @default.
• W3204652247 title "Serum Coding and Non-Coding RNAs as Biomarkers of NAFLD and Fibrosis Severity" @default.
• W3204652247 doi "https://doi.org/10.2139/ssrn.3249697" @default.
• W3204652247 hasPublicationYear "2018" @default.
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