单位：[1]Department of Cardiovascular, Shaanxi Provincial People’s Hospital, Xi’an, China,[2]Department of Cardiovascular Surgery, Yan'an Affiliated Hospital of Kunming Medical University, Kunming, China,[3]Department of Cardiovascular Surgery, China- Japan Friendship Hospital, Beijing, China,[4]Department of Cardiothoracic Surgery, Affiliated Hospital of Nantong University, Nantong, China,[5]Department of Pathology, College of Basic Medical Sciences China Medical University, Shenyang, China,[6]School of Biological Science and Medical Engineering, Beihang University, Beijing, China
Identifying biomarkers for abdominal aortic aneurysms (AAA) is key to understanding their pathogenesis, developing novel targeted therapeutics, and possibly improving patients outcomes and risk of rupture. Here, we identified AAA biomarkers from public databases using single-cell RNA-sequencing, weighted co-expression network (WGCNA), and differential expression analyses. Additionally, we used the multiple machine learning methods to identify biomarkers that differentiated large AAA from small AAA. Biomarkers were validated using GEO datasets. CIBERSORT was used to assess immune cell infiltration into AAA tissues and investigate the relationship between biomarkers and infiltrating immune cells. Therefore, 288 differentially expressed genes (DEGs) were screened for AAA and normal samples. The identified DEGs were mostly related to inflammatory responses, lipids, and atherosclerosis. For the large and small AAA samples, 17 DEGs, mostly related to necroptosis, were screened. As biomarkers for AAA, G0/G1 switch 2 (G0S2) (Area under the curve [AUC] = 0.861, 0.875, and 0.911, in GSE57691, GSE47472, and GSE7284, respectively) and for large AAA, heparinase (HPSE) (AUC = 0.669 and 0.754, in GSE57691 and GSE98278, respectively) were identified and further verified by qRT-PCR. Immune cell infiltration analysis revealed that the AAA process may be mediated by T follicular helper (Tfh) cells and the large AAA process may also be mediated by Tfh cells, M1, and M2 macrophages. Additionally, G0S2 expression was associated with neutrophils, activated and resting mast cells, M0 and M1 macrophages, regulatory T cells (Tregs), resting dendritic cells, and resting CD4 memory T cells. Moreover, HPSE expression was associated with M0 and M1 macrophages, activated and resting mast cells, Tregs, and resting CD4 memory T cells. Additional, G0S2 may be an effective diagnostic biomarker for AAA, whereas HPSE may be used to confer risk of rupture in large AAAs. Immune cells play a role in the onset and progression of AAA, which may improve its diagnosis and treatment.
基金：
This study was supported bythe Key Basic Natural Science
Foundation of Shaanxi Province (No. 2022JZ-47), Key
Industrial Innovation Chain Project in Shaanxi Province of
China (grant no. 2021ZDLSF02-03), Science and Technology
Program of Xi’an (grant no. 21YXYJ0095), Natural Science
Foundation of Shaanxi Province (No. 2022SF-476 and No.
2021SF-329), and the Open Program of Shaanxi Key
Laboratory of Integrative Traditional and Western Medicine
for Prevention and Treatment of Cardiovascular Diseases,
Shaanxi University of Chinese Medicine (grant no. 2022XXGZD-
001).
第一作者单位：[1]Department of Cardiovascular, Shaanxi Provincial People’s Hospital, Xi’an, China,[2]Department of Cardiovascular Surgery, Yan'an Affiliated Hospital of Kunming Medical University, Kunming, China,
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Xiong Tao,Lv Xiao-Shuo,Wu Gu-Jie,et al.Single-Cell Sequencing Analysis and Multiple Machine Learning Methods Identified G0S2 and HPSE as Novel Biomarkers for Abdominal Aortic Aneurysm[J].FRONTIERS in IMMUNOLOGY.2022,13:doi:10.3389/fimmu.2022.907309.
APA：
Xiong, Tao,Lv, Xiao-Shuo,Wu, Gu-Jie,Guo, Yao-Xing,Liu, Chang...&Liu, Fu-Qiang.(2022).Single-Cell Sequencing Analysis and Multiple Machine Learning Methods Identified G0S2 and HPSE as Novel Biomarkers for Abdominal Aortic Aneurysm.FRONTIERS in IMMUNOLOGY,13,
MLA：
Xiong, Tao,et al."Single-Cell Sequencing Analysis and Multiple Machine Learning Methods Identified G0S2 and HPSE as Novel Biomarkers for Abdominal Aortic Aneurysm".FRONTIERS in IMMUNOLOGY 13.(2022)
医学