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Identification of ferroptosis-related gene signatures associated with multiple sclerosis using weighted gene
Si-Chun Gu1, Can-Xing Yuan, Chao Gu
1Department of Neurology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Abstract:
Multiple sclerosis (MS) is a chronic inflammatory disease of central nervous system leading to demyelination followed by neurological symptoms. Ferroptosis is a newly discovered pathogenic hallmark important for the progression of MS. However, the gene markers of ferroptosis in MS are still uncertain. In this study, mRNA expression profiles and clinical data of MS samples were retrieved from Gene Expression Omnibus database. Weighted gene co-expression network analysis and receiver operating characteristic curve analysis were utilized to identify ferroptosis-related gene (FRG) signatures of MS. Gene set enrichment analysis and gene set variation analysis were performed to explore the biological functions of single FRG signature. HMOX1, LPCAT3 and RPL8 were firstly identified as FRG signatures of MS with the predictive capacity confirmed. Gene set enrichment analysis and gene set variation analyses revealed that metabolism-related, immune and inflammation-related, microglia-related, oxidation-related, and mitochondria-related biological functions were enriched, providing implications of the mechanisms underlying ferroptosis in MS. This study presented a systematic analysis of FRG in MS and explored the potential ferroptosis targets for new interventional strategies in MS.
Insights
This study identifies key ferroptosis-related gene signatures, HMOX1, LPCAT3, and RPL8, crucial for multiple sclerosis (MS) progression. These findings offer potential new therapeutic targets for managing MS by understanding ferroptosis mechanisms.
Area of Science:
- Neuroscience
- Immunology
- Genetics
Background:
- Multiple sclerosis (MS) is a chronic central nervous system inflammatory disease characterized by demyelination and neurological deficits.
- Ferroptosis, a distinct form of regulated cell death, is increasingly recognized as a significant contributor to MS pathogenesis.
- Identifying specific gene markers for ferroptosis in MS is crucial for understanding disease mechanisms and developing targeted therapies.
Purpose of the Study:
- To identify novel ferroptosis-related gene (FRG) signatures associated with multiple sclerosis (MS).
- To explore the biological functions and pathways enriched by these FRG signatures in MS.
- To evaluate the predictive capacity of identified FRG signatures for MS.
Main Methods:
- Utilized Gene Expression Omnibus (GEO) database for mRNA expression profiles and clinical data of MS samples.
- Applied Weighted Gene Co-expression Network Analysis (WGCNA) to identify co-expressed gene modules.
- Employed Receiver Operating Characteristic (ROC) curve analysis to assess the diagnostic and predictive value of identified genes.
- Performed Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA) to explore biological functions.
Main Results:
- Identified HMOX1, LPCAT3, and RPL8 as novel ferroptosis-related gene signatures specific to MS.
- Confirmed the significant predictive capacity of these identified FRG signatures for MS.
- Enrichment analyses revealed associations with metabolism, immune and inflammatory responses, microglia activation, oxidation, and mitochondrial function.
Conclusions:
- HMOX1, LPCAT3, and RPL8 represent key FRG signatures in MS, offering potential biomarkers.
- The identified functional enrichments highlight the involvement of metabolic, immune, oxidative, and mitochondrial pathways in MS ferroptosis.
- This systematic analysis provides a foundation for developing novel interventional strategies targeting ferroptosis in MS.
