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Updated: Jun 23, 2025
Author Spotlight: Integrated Multi-Omics Analysis for Unveiling Multicellular Immune Signatures in Clinical Heart Attack Cohorts
Published on: September 20, 2024
Unveiling shared biomarkers and therapeutic targets between systemic lupus erythematosus and heart failure through
Ting Zhou1,2, Jing Pan2, Chenghui Yan2
1Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Insights
Systemic lupus erythematosus (SLE) and heart failure (HF) share common mechanisms involving immune cell infiltration. HSP90AB1 and UBC show potential as therapeutic targets for co-occurring SLE and HF.
Area of Science:
- Immunology
- Cardiology
- Genomics
Background:
- Systemic lupus erythematosus (SLE) is associated with high mortality cardiovascular diseases, particularly heart failure (HF).
- The shared underlying mechanisms between SLE and HF remain incompletely understood.
- Identifying common pathways and therapeutic targets is crucial for managing these complex conditions.
Purpose of the Study:
- To explore shared molecular mechanisms between SLE and HF.
- To identify potential shared therapeutic targets for SLE and HF.
- To investigate the role of immune cell infiltration in the co-pathogenesis of SLE and HF.
Main Methods:
- Analysis of differentially expressed genes (DEGs) in SLE and HF datasets from NCBI GEO.
- Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genes (KEGG) pathway enrichment analyses.
- Protein-Protein Interaction (PPI) network construction and hub gene identification using Cytoscape.
- Validation of hub genes using R package 'limma', CIBERSORT algorithm for immune cell infiltration, and Weighted Gene Co-expression Network Analysis (WGCNA).
Main Results:
- 999 shared DEGs were identified, primarily enriched in Th17 cell differentiation pathways.
- Five shared hub genes (HSP90AB1, NEDD8, RPLP0, UBB, UBC) were identified and validated.
- HSP90AB1 and UBC were upregulated in failing hearts and are implicated in immune cell infiltration-mediated co-pathogenesis.
Conclusions:
- HSP90AB1 and UBC are key genes in the shared pathogenesis of SLE and HF.
- These genes are promising molecular markers for SLE and HF.
- HSP90AB1 and UBC represent potential therapeutic targets for treating patients with both SLE and HF.
Background:
Systemic lupus erythematosus (SLE) is frequently accompanied by various complications, with cardiovascular diseases being particularly concerning due to their high mortality rate. Although there is clinical evidence suggesting a potential correlation between SLE and heart failure (HF), the underlying shared mechanism is not fully understood. Therefore, it is imperative to explore the potential mechanisms and shared therapeutic targets between SLE and HF.
Methods:
The SLE and HF datasets were downloaded from the NCBI Gene Expression Omnibus database. Differentially expressed genes (DEGs) in both SLE and HF were performed using "limma" R package. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genes (KEGG) analyses were conducted to analyze the enriched functions and pathways of DEGs in both SLE and HF datasets. Protein-Protein Interaction network (PPI) and the molecular complex detection (MCODE) plugins in the Cytoscape software were performed to identify the shared hub genes between SLE and HF datasets. R package "limma" was utilized to validate the expression of hub genes based on SLE (GSE122459) and HF (GSE196656) datasets. CIBERSORT algorithm was utilized to analyze the immune cell infiltration of SLE and HF samples based on SLE (GSE112087) and HF (GSE116250) datasets. A weighted gene co-expression network analysis (WGCNA) network was established to further validate the hub genes based on HF dataset (GSE116250). Molecular biology techniques were conducted to validate the hub genes.
Results:
999 shared DGEs were identified between SLE and HF datasets, which were mainly enriched in pathways related to Th17 cell differentiation. 5 shared hub genes among the common DGEs between SLE and HF datasets were screened and validated, including HSP90AB1, NEDD8, RPLP0, UBB, and UBC. Additionally, 5 hub genes were identified in the central part of the MEbrown module, showing the strongest correlation with dilated cardiomyopathy. HSP90AB1 and UBC were upregulated in failing hearts compared to non-failing hearts, while UBB, NEDD8, and RPLP0 did not show significant changes.
Conclusion:
HSP90AB1 and UBC are closely related to the co-pathogenesis of SLE and HF mediated by immune cell infiltration. They serve as promising molecular markers and potential therapeutic targets for the treatment of SLE combined with HF.
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