ArticleLiver international : official journal of the International Association for the Study of the Liver2019
Serum coding and non-coding RNAs as biomarkers of NAFLD and fibrosis severity.
Article in Liver international : official journal of the International Association for the Study of the Liver, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 2 of them syntheses that pooled it.
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Who cites it
47 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- LncRNA and circRNA in Patients with Non-Alcoholic Fatty Liver Disease: A Systematic Review.Biomolecules · 2023Pooled it
- Epigenetic Mechanisms in Type 2 Diabetes Retinopathy: A Systematic Review.International journal of molecular sciences · 2021Pooled it
- Non-Invasive Tests for the Detection of MASLD: Biomarkers and Imaging for Staging Steatosis, MASH, and Fibrosis.International journal of general medicine · 2026Review
- Review
- Long Non-Coding RNAs in Non-Alcoholic Fatty Liver Disease; Friends or Foes?Cell biochemistry and biophysics · 2025Review
- Unraveling Metabolic Dysfunction-Associated Steatotic Liver Disease Through the Use of Omics Technologies.International journal of molecular sciences · 2025Review
- Innovative approaches to metabolic dysfunction-associated steatohepatitis diagnosis and stratification.Non-coding RNA research · 2025Article
- Noncoding RNA-Mediated Epigenetic Regulation in Hepatic Stellate Cells of Liver Fibrosis.Non-coding RNA · 2024Review
- LncRNA HOTAIR accelerates free fatty acid-induced inflammatory response in HepG2 cells by recruiting SRSF1 to stabilize MLXIPL mRNA.Cytotechnology · 2024Article
- Non-invasive diagnosis of non-alcoholic fatty liver disease: Current status and future perspective.Heliyon · 2024Review
- Two sides of the same coin: Non-alcoholic fatty liver disease and atherosclerosis.Vascular pharmacology · 2024Review
- A Nine-Gene Expression Signature Distinguished a Patient with Chronic Lymphocytic Leukemia Who Underwent Prolonged Periodic Fasting.Medicina (Kaunas, Lithuania) · 2023Article
- Identification of a New RNA and Protein Integrated Biomarker Panel Associated with Kidney Function Impairment in DKD: Translational Implications.International journal of molecular sciences · 2023Article
- Review
- Serum non-coding RNAs for diagnosis and stage of liver fibrosis.Journal of clinical laboratory analysis · 2022Review
- Mitochondrial RNAs as Potential Biomarkers of Functional Impairment in Diabetic Kidney Disease.International journal of molecular sciences · 2022Article
- Molecular Effects of Chronic Exposure to Palmitate in Intestinal Organoids: A New Model to Study Obesity and Diabetes.International journal of molecular sciences · 2022Article
- Identify Functional lncRNAs in Nonalcoholic Fatty Liver Disease by Constructing a ceRNA Network.ACS omega · 2022Article
- A robust gene expression signature for NASH in liver expression data.Scientific reports · 2022Article
- Long Noncoding RNAs and Human Liver Disease.Annual review of pathology · 2022Review
Corrections and comments
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Authors and funding
21 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND &
aimsIn patients with non-alcoholic fatty liver disease (NAFLD), liver biopsy is the gold standard to detect non-alcoholic steatohepatitis (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.
methodsWe first performed a whole transcriptome analysis through microarray (n = 12: four Control: CTRL; four mild NAFLD: NAS ≤ 4 F0; four severe NAFLD NAS ≥ 5 F3), followed by validation of selected transcripts through real-time PCRs in an independent internal cohort of 88 subjects (63 NAFLD, 25 CTRL) and in an external cohort of 50 NAFLD patients. A similar analysis was also performed on liver biopsies and HepG2 cells exposed to oleate:palmitate or only palmitate (cellular model of NAFL/NASH) at intracellular/extracellular levels. Transcript correlation with histological/clinical data was also analysed.
resultsWe identified several differentially expressed coding/non-coding RNAs in each group of the study cohort. We validated the up-regulation of UBE2V1, BNIP3L mRNAs, RP11-128N14.5 lncRNA, TGFB2/TGFB2-OT1 coding/lncRNA in patients with NAS ≥ 5 (vs NAS ≤ 4) and the up-regulation of HBA2 mRNA, TGFB2/TGFB2-OT1 coding/lncRNA in patients with Fibrosis stages = 3-4 (vs F = 0-2). In in vitro models: UBE2V1, RP11-128N14.5 and TGFB2/TGFB2-OT1 had an increasing expression trend ranging from CTRL to oleate:palmitate or only palmitate-treated cells both at intracellular and extracellular level, while BNIP3L was up-regulated only at extracellular level. UBE2V1, RP11-128N14.5, TGFB2/TGFB2-OT1 and HBA2 up-regulation was also observed at histological level. UBE2V1, RP11-128N14.5, BNIP3L and TGFB2/TGFB2-OT1 correlated with histological/biochemical data. Combinations of TGFB2/TGFB2-OT1 + Fibrosis Index based on the four factors (FIB-4) showed an Area Under the Curve (AUC) of 0.891 (P = 3.00E-06) or TGFB2/TGFB2-OT1 + Fibroscan (AUC = 0.892, P = 2.00E-06) improved the detection of F = 3-4 with respect to F = 0-2 fibrosis stages.
conclusionsWe identified specific serum coding/non-coding RNA profiles in severe and mild NAFLD patients that possibly mirror the molecular mechanisms underlying NAFLD progression towards NASH/fibrosis. TGFB2/TGFB2-OT1 detection improves FIB-4/Fibroscan diagnostic performance for advanced fibrosis discrimination.
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