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Contribution of classification based on ferroptosis-related genes to the heterogeneity of MAFLD
Xin Dai1, Rui Zhang2, Bangmao Wang3
1Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin, 300052, China.
Background:
Metabolic dysfunction-associated fatty liver disease (MAFLD) is a highly heterogeneous disease and its heterogeneity might be associated with ferroptosis because ferroptosis plays an important role in the development of MAFLD. We aimed to perform integrative analysis of ferroptosis related genes and MAFLD subtypes using bioinformatics.
Methods:
A differential expression analysis was performed to identify key ferroptosis-related genes associated with the clinical characteristics of MAFLD. Furthermore, consensus k clustering was utilized to distinguish ferroptosis-related clinical subtypes of MAFLD and assess the association of ferroptosis-related gene expression and clinical features between patients with different subtypes of MAFLD. Moreover, the variation in the immune status and regulatory relationship of ferroptosis-related genes in individuals with MAFLD was also explored using single sample gene set enrichment analysis, weighted gene coexpression network analysis and enrichment analyses.
Results:
Eight ferroptosis-related genes were identified as closely associated with both the hepatic steatosis grade and non-alcoholic fatty liver disease activity score. Two subtypes of MAFLD based on ferroptosis-related genes were identified by consensus clustering. They exhibited significantly different clinical features, immune statuses, biological processes and outcomes. The progression of the two subtypes was associated with immunity.
Conclusions:
Two highly heterogeneous subtypes of MAFLD with significantly distinct clinical features, biological processes and immune statuses were identified based on ferroptosis-associated genes, which strongly supports the hypothesis that ferroptosis plays an important role in the development of MAFLD.
Insights
This study identified two distinct subtypes of metabolic dysfunction-associated fatty liver disease (MAFLD) based on ferroptosis-related genes. These subtypes show significant differences in clinical features and immune status, highlighting ferroptosis
Area of Science:
- Hepatology
- Molecular Biology
- Bioinformatics
Background:
- Metabolic dysfunction-associated fatty liver disease (MAFLD) is a heterogeneous condition.
- Ferroptosis, a regulated cell death pathway, is implicated in MAFLD pathogenesis.
- Understanding MAFLD heterogeneity is crucial for targeted therapies.
Purpose of the Study:
- To investigate the role of ferroptosis in MAFLD heterogeneity.
- To identify distinct MAFLD subtypes based on ferroptosis-related genes.
- To analyze clinical, immune, and biological differences between MAFLD subtypes.
Main Methods:
- Differential expression analysis of ferroptosis-related genes.
- Consensus k-clustering for MAFLD subtype identification.
- Bioinformatic analyses including GSEA, WGCNA, and enrichment analyses.
Main Results:
- Eight ferroptosis-related genes correlated with hepatic steatosis grade and NAFLD activity score.
- Two MAFLD subtypes with distinct clinical features, immune profiles, and outcomes were identified.
- Subtype progression was linked to immune system variations.
Conclusions:
- Ferroptosis-associated genes define two heterogeneous MAFLD subtypes.
- These subtypes exhibit significant differences in clinical presentation and immune status.
- The findings underscore ferroptosis' critical role in MAFLD development and progression.
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