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Identification of immune-related biomarkers linked to systemic lupus erythematosus and dilated cardiomyopathy through
Gaijie Li1, Liwen Lin1, Shushu Wang1
1The First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China.
Insights
Systemic lupus erythematosus (SLE) patients often develop dilated cardiomyopathy (DCM). Researchers identified HERC6 and IFI44L genes as key diagnostic markers for SLE-related DCM, with potential therapeutic implications.
Area of Science:
- Cardiology
- Genetics
- Immunology
Background:
- Systemic lupus erythematosus (SLE) is associated with cardiac involvement, affecting up to 50% of patients.
- Dilated cardiomyopathy (DCM) is a significant concern in SLE patients, necessitating early diagnostic markers.
Purpose of the Study:
- To identify SLE-related genes contributing to DCM development.
- To discover potential biomarkers for early DCM diagnosis in SLE patients.
Main Methods:
- Utilized Gene Expression Omnibus (GEO) datasets for DCM and SLE.
- Applied differential expression analysis and weighted gene co-expression network analysis (WGCNA).
- Constructed and validated a diagnostic nomogram using machine learning and qPCR.
Main Results:
- Identified 141 key module genes and 24 differentially expressed genes common to DCM and SLE.
- HERC6 and IFI44L were identified as significant diagnostic markers for SLE-related DCM with AUC > 0.84.
- Immune dysfunction and infiltration were observed in both conditions, with HERC6 and IFI44L linked to immune cell infiltration.
Conclusions:
- HERC6 and IFI44L serve as valuable diagnostic markers for DCM in SLE patients.
- Alpha-linolenic acid shows potential as a therapeutic agent for DCM.
- The study highlights immune dysfunction as a key factor in SLE-related cardiac issues.
Background:
Epidemiological evidence indicates that up to 50% of systemic lupus erythematosus (SLE) patients exhibit cardiac involvement, suggesting a potential strong association between SLE and dilated cardiomyopathy (DCM). This study aims to identify SLE-related genes that may contribute to DCM development and to discover potential biomarkers for early DCM diagnosis in SLE patients.
Methods:
We obtained expression profile datasets for dilated cardiomyopathy DCM and SLE from the Gene Expression Omnibus (GEO) database. Through differential expression analysis and weighted gene co-expression network analysis (WGCNA), we screened for candidate biomarkers shared between DCM and SLE and constructed a diagnostic nomogram. The diagnostic performance and effectiveness of the nomogram were evaluated using external datasets and qPCR. Additionally, we performed single-gene set enrichment analysis (GSEA) on key genes to elucidate their potential roles in SLE-related DCM. Finally, we applied the CIBERSORT algorithm to assess immune cell infiltration in both DCM and SLE patients.
Results:
Through DEG and WGCNA in the DCM and SLE datasets, we identified a total of 141 key module genes and 24 commonly expressed differentially expressed genes. Enrichment analysis revealed that these 24 genes were primarily involved in inflammation, cell apoptosis, and immune regulation. Through machine learning algorithms and dataset validation, we further identified the HERC6 and IFI44L genes as important diagnostic markers for SLE-related DCM. Experimental validation supports the key role of HERC6, IFI44L, and RSAD2 in SLE-related cardiac dysfunction. Additionally, we developed a nomogram for DCM based on these two genes, and the results showed that both genes exhibited AUC values greater than 0.84. Simultaneously, single-GSEA and immune infiltration analysis indicated immune dysfunction in both DCM and SLE, with both HERC6 and IFI44L significantly associated with immune cell infiltration. Furthermore, connectivity map (cMAP) analysis identified α-linolenic acid as a potential therapeutic agent for treating DCM.
Conclusion:
Our study identifies HERC6 and IFI44L as diagnostic markers for DCM in SLE and suggests α-linolenic acid as a potential therapeutic agent.
