Identification of potential biomarkers for CAD using integration with expression and methylation data and validation by case-control study [post]

2020 unpublished
DNA methylation plays an essential role in the pathogenesis of coronary artery disease (CAD) through regulating mRNA expressions. This study aimed to identify hub genes as biomarkers functioning in CAD and regulated by DNA methylation. Methods: Gene expression and methylation datasets of peripheral blood leukocytes (PBLs) of CAD were downloaded from Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) and differentially methylated genes (DMGs) were identified based on
more » ... entified based on differentially methylated CpG sites (DMCs) in intragenic regions. The overlapped genes in DEGs and DMGs were filtered and defined as differentially expressed-methylated genes (DEMGs). Multiple computational approaches were performed to analyze the regulatory networks of DEMGs and recognize hub genes, subsequently. Finally, top hub genes were verified in a case-control study based on their differential expression levels between CAD cases and controls. Results: Totally 535 DEMGs were identified and partitioned into 4 subgroups. TSS200 and 5'UTR were confirmed as high enrichment areas of DMCs. DEMGs mainly enriched in processes of histone H3-K27 methylation, regulation of posttranscription and DNA-directed RNA polymerase activity. Pathway enrichment showed DEMGs participated in VEGF signaling pathway, adipocytokine signaling pathway and PI3K-Akt signaling pathway. Besides, hub genes FN1 (fibronectin 1), PTEN (phosphatase and tensin homolog), POLR3A (RNA polymerase III subunit A) were experimentally proved discordantly expressed in CAD patients when compared with controls. Conclusions: In conclusion, our study demonstrated the probable functional genes of PBLs in CAD, in which FN1, PTEN and POLR3A were confirmed. The underlying mechanism that differential expressionmethylation of FN1, PTEN and POLR3A in CAD need further study. Background Coronary artery disease (CAD), as the main type of cardiovascular diseases, has become one of the leading causes of morbidity and mortality in both developed and developing countries [1] . And the circumstance shows an acuter tendency recently due to the population aging. According to the CAD prediction model, more than 20 million deaths and 16 million labor loss will be attributed to CAD from
doi:10.21203/rs.2.23331/v1 fatcat:gdwf5mb3pvaordt62dchloz3ju