Systems biology-based analysis exploring shared biomarkers and pathogenesis of myocardial infarction combined with osteoarthritis.

Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101560960 Publication Model: eCollection Cited Medium: Internet ISSN: 1664-3224 (Electronic) Linking ISSN: 16643224 NLM ISO Abbreviation: Front Immunol Subsets: MEDLINE

Original Publication: [Lausanne : Frontiers Research Foundation]

Myocardial Infarction*/genetics ; Myocardial Infarction*/immunology ; Osteoarthritis*/genetics ; Osteoarthritis*/metabolism ; Systems Biology* ; Biomarkers* ; Gene Regulatory Networks* ; Protein Interaction Maps* ; Gene Expression Profiling*; Humans ; Databases, Genetic ; Transcriptome ; Chondrocytes/metabolism ; Chondrocytes/immunology ; Myocytes, Cardiac/metabolism ; Myocytes, Cardiac/pathology ; Animals ; Computational Biology/methods

Background: More and more evidence supports the association between myocardial infarction (MI) and osteoarthritis (OA). The purpose of this study is to explore the shared biomarkers and pathogenesis of MI complicated with OA by systems biology.
Methods: Gene expression profiles of MI and OA were downloaded from the Gene Expression Omnibus (GEO) database. The Weighted Gene Co-Expression Network Analysis (WGCNA) and differentially expressed genes (DEGs) analysis were used to identify the common DEGs. The shared genes related to diseases were screened by three public databases, and the protein-protein interaction (PPI) network was built. GO and KEGG enrichment analyses were performed on the two parts of the genes respectively. The hub genes were intersected and verified by Least absolute shrinkage and selection operator (LASSO) analysis, receiver operating characteristic (ROC) curves, and single-cell RNA sequencing analysis. Finally, the hub genes differentially expressed in primary cardiomyocytes and chondrocytes were verified by RT-qPCR. The immune cell infiltration analysis, subtypes analysis, and transcription factors (TFs) prediction were carried out.
Results: In this study, 23 common DEGs were obtained by WGCNA and DEGs analysis. In addition, 199 common genes were acquired from three public databases by PPI. Inflammation and immunity may be the common pathogenic mechanisms, and the MAPK signaling pathway may play a key role in both disorders. DUSP1, FOS, and THBS1 were identified as shared biomarkers, which is entirely consistent with the results of single-cell RNA sequencing analysis, and furher confirmed by RT-qPCR. Immune infiltration analysis illustrated that many types of immune cells were closely associated with MI and OA. Two potential subtypes were identified in both datasets. Furthermore, FOXC1 may be the crucial TF, and the relationship of TFs-hub genes-immune cells was visualized by the Sankey diagram, which could help discover the pathogenesis between MI and OA.
Conclusion: In summary, this study first revealed 3 (DUSP1, FOS, and THBS1) novel shared biomarkers and signaling pathways underlying both MI and OA. Additionally, immune cells and key TFs related to 3 hub genes were examined to further clarify the regulation mechanism. Our study provides new insights into shared molecular mechanisms between MI and OA.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2024 Luo, Liu, Xue, He, Lv and Zhao.)

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Keywords: MAPK signaling pathway; biomarkers; immune cell infiltration; myocardial infarction; osteoarthritis; systems biology

0 (Biomarkers)

Date Created: 20240801 Date Completed: 20240801 Latest Revision: 20240802

20240802

PMC11288954

10.3389/fimmu.2024.1398990

39086489