AUTHOR=Wang Lihong , He Wenhui , Wang Xilin , Wang Jianrong , Wei Xiaojuan , Wu Dongzhi , Wu Yundan 

TITLE=Potential diagnostic markers shared between non-alcoholic fatty liver disease and atherosclerosis determined by machine learning and bioinformatic analysis

JOURNAL=Frontiers in Medicine

VOLUME=11

YEAR=2024

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2024.1322102

DOI=10.3389/fmed.2024.1322102

ISSN=2296-858X

ABSTRACT=<sec><title>Background</title><p>Evidence indicates that chronic non-alcoholic fatty liver disease (NAFLD) can increase the risk of atherosclerosis (AS), but the underlying mechanism remains unclear.</p></sec><sec><title>Objective</title><p>This study is intended for confirming key genes shared between NAFLD and AS, and their clinical diagnostic value to establish a foundation for searching novel therapeutic targets.</p></sec><sec><title>Methods</title><p>We downloaded the Gene Expression Omnibus (GEO) datasets, GSE48452 and GSE89632 for NAFLD and GSE100927, GSE40231 and GSE28829 for AS. The progression of NAFLD co-expression gene modules were recognized via weighted gene co-expression network analysis (WGCNA). We screened for differentially expressed genes (DEGs) associated with AS and identified common genes associated with NAFLD and AS using Venn diagrams. We investigated the most significant core genes between NAFLD and AS using machine learning algorithms. We then constructed a diagnostic model by creating a nomogram and evaluating its performance using ROC curves. Furthermore, the CIBERSORT algorithm was utilized to explore the immune cell infiltration between the two diseases, and evaluate the relationship between diagnostic genes and immune cells.</p></sec><sec><title>Results</title><p>The WGCNA findings associated 1,129 key genes with NAFLD, and the difference analysis results identified 625 DEGs in AS, and 47 genes that were common to both diseases. We screened the core <italic>RPS6KA1</italic> and <italic>SERPINA3</italic> genes associated with NAFLD and AS using three machine learning algorithms. A nomogram and ROC curves demonstrated that these genes had great clinical meaning. We found differential expression of <italic>RPS6KA1</italic> in patients with steatosis and NASH, and of <italic>SERPINA3</italic> only in those with NASH compared with normal individuals. Immune infiltration findings revealed that macrophage and mast cell infiltration play important roles in the development of NAFLD and AS. Notably, <italic>SERPINA3</italic> correlated negatively, whereas <italic>RPS6KA1</italic> correlated positively with macrophages and mast cells.</p></sec><sec><title>Conclusion</title><p>We identified <italic>RPS6KA1</italic> and <italic>SERPINA3</italic> as potential diagnostic markers for NAFLD and AS. The most promising marker for a diagnosis of NAFLD and AS might be <italic>RPS6KA1</italic>, whereas <italic>SERPINA3</italic> is the most closely related gene for NASH and AS. We believe that further exploration of these core genes will reveal the etiology and a pathological relationship between NAFLD and AS.</p></sec>