Identification of mitochondria-related biomarkers in liver fibrosis via interpretable machine learning and WGCNA: transcriptomic analysis and In Vivo validation - Report - MDSpire

Identification of mitochondria-related biomarkers in liver fibrosis via interpretable machine learning and WGCNA: transcriptomic analysis and In Vivo validation

  • By

  • Yupeng Ma

  • Xinhong Chen

  • Lujin Yin

  • Yongbin Chi

  • Denghai Zhang

  • Xiaocheng Xue

  • Xue Zhang

  • May 28, 2026

  • 0 min

Share

Clinical Report: Discovery of Mitochondrial Biomarkers Linked to Liver Fibrosis

Overview

This study identifies key mitochondrial biomarkers associated with liver fibrosis, emphasizing the role of ACOT9, ALDH1B1, and PCK2 in fibrogenesis. The findings suggest potential therapeutic targets for intervention in chronic liver diseases.

Background

Hepatic fibrosis is a critical stage in chronic liver diseases, necessitating timely intervention to prevent progression to cirrhosis and hepatocellular carcinoma. Mitochondrial dysfunction has emerged as a significant factor in fibrogenesis, highlighting the need for biomarkers that can guide treatment strategies. Understanding the molecular mechanisms underlying liver fibrosis is essential for developing effective therapeutic interventions.

Data Highlights

GeneExpression PatternRole
ACOT9Upregulated in fibrotic liver tissueRegulator of fibrotic markers
ALDH1B1Predominantly in hepatocytesAssociated with fibrogenesis
PCK2In cholangiocytes/HSCsInvolved in fibrosis

Key Findings

  • 38 mitochondria-related DEGs were identified in CCl4-induced fibrosis.
  • Machine learning prioritized ACOT9, ALDH1B1, and PCK2 as key mitochondrial targets.
  • ACOT9 was significantly upregulated in human cirrhosis datasets.
  • Silencing ACOT9 in LX-2 cells downregulated classical fibrotic markers.
  • CellChat analysis indicated remodeling of TGF-β and COLLAGEN signaling networks.

Clinical Implications

The identification of ACOT9 as a key regulator in liver fibrosis suggests it may serve as a novel therapeutic target. Clinicians should consider the potential of mitochondrial biomarkers in assessing liver disease progression and guiding treatment decisions.

Conclusion

The study underscores the importance of mitochondrial biomarkers in liver fibrosis and highlights ACOT9's potential as a therapeutic target. Further research is warranted to explore its clinical applications.

Related Resources & Content

  1. npj Digital Medicine, 2026 -- Combining Multi-Omics Approaches with Machine Learning to Unravel Cellular Diversity and Fibrotic Regulatory Pathways in the Transition from MASLD to MASH
  2. The ASCO Post, 2026 -- AI-Backed Liquid Biopsies Identify Liver Diseases
  3. EASL–EASD–EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD): Executive Summary - PMC
  4. Circulating Fibroblast Growth Factor-21 in Patients with Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis - PubMed
  5. The ASCO Post — AI-Backed Liquid Biopsies Identify Liver Diseases
  6. The ASCO Post — AI-Backed Liquid Biopsies Identify Liver Diseases
  7. EASL–EASD–EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD): Executive Summary - PMC
  8. Circulating Fibroblast Growth Factor-21 in Patients with Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis - PubMed

Original Source(s)

Related Content