Association of Epigenetic Aging Biomarkers With Risk of MASLD-Related HCC

Area of Science:

• Biomarkers and diagnostics
• Genomics and epigenetics
• Liver disease research

Background:

• Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing cause of hepatocellular carcinoma (HCC).
• The mechanisms linking MASLD to HCC are not fully understood.
• Epigenetic aging biomarkers are associated with age-related diseases, but their role in MASLD-HCC is unknown.

Purpose of the Study:

• To investigate the association between five epigenetic aging biomarkers and the risk of developing MASLD-HCC.
• To determine if epigenetic aging can serve as a predictive marker for MASLD-HCC.

Main Methods:

• Whole blood DNA methylation was analyzed using an Infinium 850k array.
• Principal components-based (PC) versions of HorvathAge, HannumAge, PhenoAge, GrimAge, and DunedinPACE aging rate were calculated.
• Logistic regression was used to assess associations between aging biomarkers and MASLD-HCC risk, calculating odds ratios (ORs) and 95% confidence intervals (CIs).

Main Results:

• Higher relative age accelerations of PCPhenoAge, PCGrimAge, and DunedinPACE were significantly associated with an increased risk of MASLD-HCC.
• PCPhenoAge (continuous OR=1.04), PCGrimAge (continuous OR=1.16), and DunedinPACE (continuous OR=1.72) showed significant associations with MASLD-HCC risk.
• PCHorvathAge and PCHannumAge were not significantly associated with MASLD-HCC risk.

Conclusions:

• Accelerated epigenetic aging, specifically indicated by PCPhenoAge, PCGrimAge, and DunedinPACE, is associated with an elevated risk of MASLD-HCC.
• These epigenetic aging biomarkers show potential for improving risk assessment and stratification in patients with MASLD.
• Further research could integrate these biomarkers into clinical practice for early detection and management of MASLD-HCC.