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Exploring the common mechanisms and biomarker ST8SIA4 of atherosclerosis and ankylosing spondylitis through
Yirong Ma1, Junyu Lai2, Qiang Wan2
1Department of Postgraduate, Jiangxi University of Traditional Chinese Medicine, Nanchang, China.
Insights
This study identifies ST8SIA4 as a common diagnostic biomarker for atherosclerosis and ankylosing spondylitis, revealing shared pathways and immune microenvironment interactions. These findings offer potential for improved diagnostics and understanding of these related conditions.
Area of Science:
- Biomedical research
- Bioinformatics
- Genomics
Background:
- Atherosclerosis (AS) is a significant cause of cardiovascular and cerebrovascular events.
- Ankylosing spondylitis frequently co-occurs with AS, suggesting shared underlying mechanisms.
- The precise pathogenic links between AS and ankylosing spondylitis remain unclear.
Purpose of the Study:
- To identify common diagnostic biomarkers and molecular pathways shared by atherosclerosis and ankylosing spondylitis.
- To elucidate the role of identified biomarkers in disease pathogenesis.
- To explore the interaction of key biomarkers with the immune microenvironment.
Main Methods:
- Utilized bioinformatics approaches on Gene Expression Omnibus (GEO) datasets for AS and ankylosing spondylitis.
- Applied Limma R package for differential gene expression (DEG) analysis and WGCNA for module identification.
- Employed SVM-RFE for biomarker selection, validated with ROC analysis, and investigated immune microenvironment interactions using CIBERSORT and single-cell analysis.
Main Results:
- Identified 71 overlapping genes between AS DEGs and ankylosing spondylitis module genes.
- Confirmed ST8SIA4 as a common diagnostic marker, upregulated in both diseases with robust diagnostic utility.
- Revealed ST8SIA4's association with the immune microenvironment and expression in immune cells like Macrophages, Monocytes, and T cells.
Conclusions:
- ST8SIA4 serves as a potential common diagnostic gene for atherosclerosis and ankylosing spondylitis.
- The study highlights the involvement of the lysosomal pathway and immune interactions in shared pathogenesis.
- Findings provide insights into potential diagnostic strategies and therapeutic targets for both conditions.
Background:
Atherosclerosis (AS) is a major contributor to cerebrovascular and cardiovascular events. There is growing evidence that ankylosing spondylitis is closely linked to AS, often co-occurring with it; however, the shared pathogenic mechanisms between the two conditions are not well understood. This study employs bioinformatics approaches to identify common biomarkers and pathways between AS and ankylosing spondylitis.
Methods:
Gene expression datasets for AS (GSE100927, GSE28829, GSE155512) and ankylosing spondylitis (GSE73754, GSE25101) were obtained from the Gene Expression Omnibus (GEO). Differential expression genes (DEGs) and module genes for AS and ankylosing spondylitis were identified using the Limma R package and weighted gene co-expression network analysis (WGCNA) techniques, respectively. The machine learning algorithm SVM-RFE was applied to pinpoint promising biomarkers, which were then validated in terms of their expression levels and diagnostic efficacy in AS and ankylosing spondylitis, using two separate GEO datasets. Furthermore, the interaction of the key biomarker with the immune microenvironment was investigated via the CIBERSORT algorithm, single-cell analysis was used to identify the locations of common diagnostic markers.
Results:
The dataset GSE100927 contains 524 DEGs associated with AS, whereas dataset GSE73754 includes 1,384 genes categorized into modules specific to ankylosing spondylitis. Analysis of these datasets revealed an overlap of 71 genes between the DEGs of AS and the modular genes of ankylosing spondylitis. Utilizing the SVM-RFE algorithm, 15 and 24 central diagnostic genes were identified in datasets GSE100927 and GSE73754, respectively. Further validation of six key genes using external datasets confirmed ST8SIA4 as a common diagnostic marker for both conditions. Notably, ST8SIA4 is upregulated in samples from both diseases. Additionally, ROC analysis confirmed the robust diagnostic utility of ST8SIA4. Moreover, analysis through CIBERSORT suggested an association of the ST8SIA4 gene with the immune microenvironment in both disease contexts. Single-cell analysis revealed that ST8SIA4 is primarily expressed in Macrophages, Monocytes, T cells, and CMPs.
Conclusion:
This study investigates the role of ST8SIA4 as a common diagnostic gene and the involvement of the lysosomal pathway in both AS and ankylosing spondylitis. The findings may yield potential diagnostic biomarkers and offer new insights into the shared pathogenic mechanisms underlying these conditions.
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