Distinct Morphological and Molecular Profiles of NAFLD and NAFLD-associated HCC Revealed by Immunohistochemistry and MicroRNA Analysis

J Gastrointestin Liver Dis. 2023 Sep 28;32(3):356-366. doi: 10.15403/jgld-5065.

Abstract

Background and aims: Non-alcoholic fatty liver disease (NAFLD) is a common hepatic condition that can progress to hepatocellular carcinoma (HCC) in non-cirrhotic livers. To better understand the development of NAFLD-associated HCC, we performed an integrated morphological and molecular analysis to identify new insights that can improve the follow-up of NAFLD patients.

Methods: Our study included a cohort of 14 NAFLD-associated HCC and 41 NAFLD patients. We analyzed clinical parameters, a four-microRNA (miRNA) panel (miR-21-5p, miR-34a-5p, miR-130a-3p, and miR-155-3p) panel and their relationship with p53 and β-catenin expression.

Results: In the study cohort, the NAFLD-associated HCC patients were predominantly male, older, had significantly altered hepatic function, and a higher incidence of hypertension, type 2 diabetes, and dyslipidemia. Morphologically, the NAFLD-HCC group had substantially higher steatosis, ballooning, and fibrosis grades than the NAFLD group. The β-catenin expression was higher in both adjacent non-tumoral liver tissue (ANT) from NAFLD-associated HCC patients and in HCC tissue com-pared with NAFLD samples. The 4 miRNAs panel showed a dysregulated expression profile between NAFLD, ANT and HCC samples.

Conclusions: This study provides important insights regarding the molecular mechanisms underlying HCC progression in NAFLD patients, allowing for the development of better screening strategies for the early detection of NAFLD-associated HCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Hepatocellular* / diagnosis
  • Carcinoma, Hepatocellular* / epidemiology
  • Carcinoma, Hepatocellular* / genetics
  • Diabetes Mellitus, Type 2* / complications
  • Female
  • Humans
  • Immunohistochemistry
  • Liver Neoplasms* / diagnosis
  • Liver Neoplasms* / epidemiology
  • Liver Neoplasms* / genetics
  • Male
  • MicroRNAs* / genetics
  • Non-alcoholic Fatty Liver Disease* / complications
  • Non-alcoholic Fatty Liver Disease* / diagnosis
  • Non-alcoholic Fatty Liver Disease* / genetics
  • beta Catenin / genetics

Substances

  • MicroRNAs
  • beta Catenin