Identification of potential therapeutic targets for plaque vulnerability based on an integrated analysis

Liu Miao; Yue-Ai Qin; Zhi-Jie Yang; Wan-Xin Shi; Xin-Qiao Wei; Yuan Liu; Yan-Li Liu

doi:10.1016/j.numecd.2024.02.005

Identification of potential therapeutic targets for plaque vulnerability based on an integrated analysis

Nutr Metab Cardiovasc Dis. 2024 Feb 17:S0939-4753(24)00076-0. doi: 10.1016/j.numecd.2024.02.005. Online ahead of print.

Authors

Liu Miao¹, Yue-Ai Qin², Zhi-Jie Yang³, Wan-Xin Shi⁴, Xin-Qiao Wei⁵, Yuan Liu⁶, Yan-Li Liu⁷

Affiliations

¹ Department of Cardiology, Liuzhou People's Hospital, Affiliated of Guangxi Medical University, 8 Wenchang Road, Liuzhou 545006, Guangxi, China; The Key Laboratory of Coronary Atherosclerotic Disease Prevention and Treatment of Liuzhou, China. Electronic address: dr.miaoliu@qq.com.
² Department of Cardiology, Liuzhou People's Hospital, Affiliated of Guangxi Medical University, 8 Wenchang Road, Liuzhou 545006, Guangxi, China; The Key Laboratory of Coronary Atherosclerotic Disease Prevention and Treatment of Liuzhou, China. Electronic address: 46493637@qq.com.
³ Department of Cardiology, Liuzhou People's Hospital, Affiliated of Guangxi Medical University, 8 Wenchang Road, Liuzhou 545006, Guangxi, China; The Key Laboratory of Coronary Atherosclerotic Disease Prevention and Treatment of Liuzhou, China. Electronic address: yfyyzj@163.com.
⁴ Department of Cardiology, Liuzhou People's Hospital, Affiliated of Guangxi Medical University, 8 Wenchang Road, Liuzhou 545006, Guangxi, China; The Key Laboratory of Coronary Atherosclerotic Disease Prevention and Treatment of Liuzhou, China. Electronic address: jiuwanly2233@hotmail.com.
⁵ Department of Cardiology, Liuzhou People's Hospital, Affiliated of Guangxi Medical University, 8 Wenchang Road, Liuzhou 545006, Guangxi, China; The Key Laboratory of Coronary Atherosclerotic Disease Prevention and Treatment of Liuzhou, China. Electronic address: 1075626774@qq.com.
⁶ Department of Cardiology, Liuzhou People's Hospital, Affiliated of Guangxi Medical University, 8 Wenchang Road, Liuzhou 545006, Guangxi, China; The Key Laboratory of Coronary Atherosclerotic Disease Prevention and Treatment of Liuzhou, China. Electronic address: 2014855319@qq.com.
⁷ Department of Cardiology, Liuzhou People's Hospital, Affiliated of Guangxi Medical University, 8 Wenchang Road, Liuzhou 545006, Guangxi, China; The Key Laboratory of Coronary Atherosclerotic Disease Prevention and Treatment of Liuzhou, China. Electronic address: gxlyl@126.com.

PMID: 38749785
DOI: 10.1016/j.numecd.2024.02.005

Abstract

Background and aims: This study aimed to explore potential hub genes and pathways of plaque vulnerability and to investigate possible therapeutic targets for acute coronary syndrome (ACS).

Methods and results: Four microarray datasets were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs), weighted gene coexpression networks (WGCNA) and immune cell inﬁltration analysis (IIA) were used to identify the genes for plaque vulnerability. Then, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, Disease Ontology, Gene Ontology annotation and protein-protein interaction (PPI) network analyses were performed to explore the hub genes. Random forest and artiﬁcial neural networks were constructed for validation. Furthermore, the CMap and Herb databases were employed to explore possible therapeutic targets. A total of 168 DEGs with an adjusted P < 0.05 and approximately 1974 IIA genes were identified in GSE62646. Three modules were detected and associated with CAD-Class, including 891 genes that can be found in GSE90074. After removing duplicates, 114 hub genes were used for functional analysis. GO functions identified 157 items, and 6 pathways were enriched for the KEGG pathway at adjusted P < 0.05 (false discovery rate, FDR set at < 0.05). Random forest and artificial neural network models were built based on the GSE48060 and GSE34822 datasets, respectively, to validate the previous hub genes. Five genes (GZMA, GZMB, KLRB1, KLRD1 and TRPM6) were selected, and only two of them (GZMA and GZMB) were screened as therapeutic targets in the CMap and Herb databases.

Conclusion: We performed a comprehensive analysis and validated GZMA and GZMB as a target for plaque vulnerability, which provides a therapeutic strategy for the prevention of ACS. However, whether it can be used as a predictor in blood samples requires further experimental verification.

Keywords: CMap and Herb databases; Immune cell inﬁltration analysis; Integrated analysis; Plaque vulnerability; Random forest and artiﬁcial neural network.