AUTHOR=Jin Pengyue , Zhang Shangyu , Yang Li , Zeng Yujie , Li Yongguo , Tang Renkuan 

TITLE=Analysis and validation of biomarkers and immune cell infiltration profiles in unstable coronary atherosclerotic plaques using bioinformatics and machine learning

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=Volume 12 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2025.1451255

DOI=10.3389/fcvm.2025.1451255

ISSN=2297-055X

ABSTRACT=IntroductionDecreased stability of coronary atherosclerotic plaques correlates with a heightened risk of acute coronary syndrome (ACS). Thus, early diagnosis and treatment of unstable plaques are imperative in averting adverse cardiovascular events. This study aims to identify diagnostic biomarkers for unstable coronary atherosclerotic plaques and investigate the role of immune cell infiltration in their formation.MethodsThe datasets GSE163154 and GSE111782, obtained from the gene expression omnibus (GEO) database, were amalgamated for bioinformatics analysis, using the dataset GSE43292 as a test set. Sequentially, we performed principal component analysis (PCA), differential gene expression analysis, enrichment analysis, weighted gene co-expression network analysis (WGCNA), utilized a machine learning algorithm to screen key genes, conducted receiver operating characteristic (ROC) curve analysis and nomogram model to assess biomarker diagnostic efficacy, validated the biomarkers, and analyzed immune cell infiltration.ResultsIn conclusion, enrichment analyses demonstrate that genes are significantly enriched in inflammatory and immune-related pathways. We identified HSPA2 and GEM as key genes and validated them experimentally. Significant differences existed in immune cell infiltration between subgroups. Additionally, HSPA2 and GEM showed significant associations with a wide range of immune cells.DiscussionHSPA2 and GEM can function as diagnostic biomarkers for unstable coronary atherosclerotic plaques. In combination with immune cell infiltration analyses, our study provides new insights into the future study of unstable plaque occurrence and molecular mechanisms.