Key result
HSPA9 and SOD2 emerge as highly diagnostic aging-related genes for AF in aged canine models.
Why the study?
Aging plays an essential role in the occurrence and development of AF, but the specific aging-related genes associated with AF remained to be identified.
Effect estimate: AUC 0.986 (HSPA9) and 0.961 (SOD2)
Bioinformatics analysis and canine model validation identified HSPA9 and SOD2 as key aging-related genes and potential diagnostic biomarkers in atrial fibrillation.
Hypothesis-generating for HSPA9/SOD2 as AF biomarkers; requires human validation before clinical consideration.
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in the clinic. Aging plays an essential role in the occurrence and development of AF. Herein, we aimed to identify the aging-related genes associated with AF using bioinformatics analysis. Transcriptome profiles of AF were obtained from the GEO database. Differential expression analysis was performed to identify AF-specific aging-related genes. GO and KEGG enrichment analyses were performed. Subsequently, the LASSO, SVM-RFE, and MCC algorithms were applied to screen aging-related genes. The mRNA expression of the screened genes was validated in the left atrial samples of aged rapid atrial pacing-induced AF canine models and their counterparts. The ROC curves of them were drawn to evaluate their diagnostic potential. Moreover, CIBERSORT was used to estimate immune infiltration. A correlation analysis between screened aging-related genes and infiltrating immune cells was performed. A total of 24 aging-related genes were identified, which were found to be mainly involved in the FoxO signaling pathway, PI3K-Akt signaling pathway, longevity regulating pathway, and peroxisome according to functional enrichment analysis. LASSO, SVM-RFE, and MCC algorithms identified three genes (HSPA9, SOD2, TXN). Furthermore, the expression levels of HSPA9 and SOD2 were validated in aged rapid atrial pacing-induced AF canine models. HSPA9 and SOD2 could be potential diagnostic biomarkers for AF, as evidenced by the ROC curves. Immune infiltration and correlation analysis revealed that HSPA9 and SOD2 were related to immune cell infiltrates. Collectively, these findings provide novel insights into the potential aging-related genes associated with AF. HSPA9 and SOD2 may play a significant role in the occurrence and development of AF.
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Zhou et al. (2023) studied Atrial fibrillation (n=32). Rapid atrial pacing (canine model) vs. Sham-operated / Sinus rhythm was evaluated on Diagnostic efficacy (Area Under the Curve) of HSPA9 and SOD2 for atrial fibrillation (AUC 0.986 (HSPA9) and 0.961 (SOD2)). Bioinformatics analysis and validation in aged canine models identified HSPA9 and SOD2 as key aging-related genes with high diagnostic potential for atrial fibrillation.
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