AUTHOR=Jiang Meiling , Zhao Weidong , Wu Liyong , Zhu Guofu 

TITLE=Screening of m6A-associated ferroptosis-related genes in atherosclerosis based on WGCNA

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=11

YEAR=2024

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2024.1469805

DOI=10.3389/fcvm.2024.1469805

ISSN=2297-055X

ABSTRACT=<sec><title>Background</title><p>N6-methyladenosine (m6A) has been shown to mediate ferroptosis but its role in atherosclerosis (AS) is unclear.</p></sec><sec><title>Methods</title><p>Differentially expressed m6A-associated ferroptosis-related genes (DE-m6A-Ferr-RGs) were obtained using differential expression analysis and Pearson correlation analysis. Weighted gene co-expression network analysis (WGCNA) was also performed. The intersection of the module genes and the DE-m6A-Ferr-RGs were recorded as candidate m6A-Ferr-related signature genes. Finally, the m6A-Ferr-related signature genes were screened using least absolute shrinkage and selection operator (LASSO) analysis. Expression validation, receiver operating characteristic ( mapping, and immune correlation analysis were also performed based on the m6A-Ferr-related signature genes. The expression of m6A-Ferr-related signature genes was further validated using a real-time polymerase chain reaction (RT-qPCR).</p></sec><sec><title>Results</title><p>In total, 6,167 differentially expressed genes were intersected with 24 m6A- and 259 ferroptosis-related genes, respectively, resulting in 113 DE-m6A-Ferr-RGs obtained using Pearson’s correlation analysis. The module genes obtained from the WGCNA and the 113 DE-m6A-Ferr-RGs were intersected to obtain 48 candidate m6A-Ferr-related signature genes. LASSO analysis was performed and six m6A-Ferr-related signature genes were screened. In addition, the area under the curve values of all six m6A-Ferr-related signature genes were greater than 0.7, indicating that they had potential diagnostic value. Furthermore, the RT-qPCR results revealed that the expression of <italic>SLC3A2</italic>, <italic>NOX4</italic>, and <italic>CDO1</italic> was consistent with the transcriptome level. Moreover, there was a significant difference in two types of immune cells between the AS and control groups. Naive B cells, CD8+ T cells, regulatory T cells, and activated natural killer cells were positively correlated with <italic>CDO1</italic> and <italic>NOX4</italic> but negatively correlated with <italic>ATG7</italic>, <italic>CYBB</italic>, and <italic>SLC3A2</italic>.</p></sec><sec><title>Conclusion</title><p>In total, three m6A-Ferr-related signature genes (<italic>NOX4</italic>, <italic>CDO1</italic>, and <italic>SLC3A2</italic>) were obtained through a series of bioinformatics analyses and an RT-qPCR.</p></sec>