Identification of immune cell infiltration and diagnostic biomarkers in unstable atherosclerotic plaques by integrated bioinformatics analysis and machine learningстатья из журнала
Аннотация: Objective The decreased stability of atherosclerotic plaques increases the risk of ischemic stroke. However, the specific characteristics of dysregulated immune cells and effective diagnostic biomarkers associated with stability in atherosclerotic plaques are poorly characterized. This research aims to investigate the role of immune cells and explore diagnostic biomarkers in the formation of unstable plaques for the sake of gaining new insights into the underlying molecular mechanisms and providing new perspectives for disease detection and therapy. Method Using the CIBERSORT method, 22 types of immune cells between stable and unstable carotid atherosclerotic plaques from RNA-sequencing and microarray data in the public GEO database were quantitated. Differentially expressed genes (DEGs) were further calculated and were analyzed for enrichment of GO Biological Process and KEGG pathways. Important cell types and hub genes were screened using machine learning methods including least absolute shrinkage and selection operator (LASSO) regression and random forest. Single-cell RNA sequencing and clinical samples were further used to validate critical cell types and hub genes. Finally, the DGIdb database of gene–drug interaction data was utilized to find possible therapeutic medicines and show how pharmaceuticals, genes, and immune cells interacted. Results A significant difference in immune cell infiltration was observed between unstable and stable plaques. The proportions of M0, M1, and M2 macrophages were significantly higher and that of CD8 + T cells and NK cells were significantly lower in unstable plaques than that in stable plaques. With respect to DEGs, antigen presentation genes (CD74, B2M, and HLA-DRA), inflammation-related genes (MMP9, CTSL, and IFI30), and fatty acid-binding proteins (CD36 and APOE) were elevated in unstable plaques, while the expression of smooth muscle contraction genes (TAGLN, ACAT2, MYH10, and MYH11) was decreased in unstable plaques. M1 macrophages had the highest instability score and contributed to atherosclerotic plaque instability. CD68, PAM, and IGFBP6 genes were identified as the effective diagnostic markers of unstable plaques, which were validated by validation datasets and clinical samples. In addition, insulin, nivolumab, indomethacin, and α-mangostin were predicted to be potential therapeutic agents for unstable plaques. Conclusion M1 macrophages is an important cause of unstable plaque formation, and CD68, PAM, and IGFBP6 could be used as diagnostic markers to identify unstable plaques effectively.
Год издания: 2022
Авторы: Jing Wang, Zijian Kang, Yandong Liu, Zifu Li, Yang Liu, Jianmin Liu
Издательство: Frontiers Media
Источник: Frontiers in Immunology
Ключевые слова: Atherosclerosis and Cardiovascular Diseases, Single-cell and spatial transcriptomics, Immune cells in cancer
Другие ссылки: Frontiers in Immunology (PDF)
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DOAJ (DOAJ: Directory of Open Access Journals) (HTML)
PubMed Central (HTML)
PubMed (HTML)
Frontiers in Immunology (HTML)
DOAJ (DOAJ: Directory of Open Access Journals) (HTML)
PubMed Central (HTML)
PubMed (HTML)
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Том: 13