Identification of CDKN1A as a potential key risk factor in MASLD progression

Area of Science:

• Hepatology
• Molecular Biology
• Genomics

Background:

• Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly NAFLD, is a heterogeneous liver condition with unclear progression mechanisms.
• Lack of reliable diagnostic markers and effective treatments hinders MASLD management.
• Understanding MASLD pathogenesis is crucial for developing targeted therapies.

Purpose of the Study:

• To identify key genes involved in MASLD progression.
• To investigate the role of CDKN1A in MASLD pathogenesis.
• To evaluate CDKN1A as a potential diagnostic biomarker and therapeutic target for MASLD.

Main Methods:

• Differential gene expression analysis of public MASLD datasets (GSE126848, GSE135251) using DESeq2 and edgeR.
• Protein-protein interaction network analysis to identify hub genes.
• Validation of CDKN1A expression in MASLD patient liver samples and animal models (HFD, ob/ob, db/db mice).
• Correlation analysis of CDKN1A levels with MASLD severity, NAS, and fibrosis stage.

Main Results:

• 52 differentially expressed genes (DEGs) were identified in MASLD.
• Top 10 hub genes were identified through PPI network analysis.
• CDKN1A was the sole consistently upregulated gene in MASLD across multiple datasets and validated at protein level.
• CDKN1A mRNA and protein levels were significantly elevated in MASLD patients and animal models.
• CDKN1A expression correlated positively with MASLD severity, NAS, and fibrosis stage.

Conclusions:

• CDKN1A is significantly upregulated in MASLD and its levels correlate with disease severity.
• CDKN1A shows potential as a promising biomarker for MASLD diagnosis and prognosis.
• CDKN1A may represent a novel therapeutic target for MASLD, warranting further investigation into its pathological role.