Comprehensive bioinformatics analysis revealed potential key genes and pathways underlying abdominal aortic aneurysm

Kaijie Zhang; Jianing Yue; Li Yin; Jinyi Chen; Yunlu Chen; Lanting Hu; Jian Shen; Naiji Yu; Yunxia Gong; Zhenjie Liu

doi:10.1016/j.csbj.2023.10.052

Comprehensive bioinformatics analysis revealed potential key genes and pathways underlying abdominal aortic aneurysm

Comput Struct Biotechnol J. 2023 Nov 2:21:5423-5433. doi: 10.1016/j.csbj.2023.10.052. eCollection 2023.

Authors

Kaijie Zhang¹, Jianing Yue², Li Yin¹, Jinyi Chen¹, Yunlu Chen³, Lanting Hu¹, Jian Shen⁴, Naiji Yu¹, Yunxia Gong¹, Zhenjie Liu¹

Affiliations

¹ Department of Vascular Surgery, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province 310009, China.
² Department of Vascular Surgery, Zhongshan Hospital of Fudan University School of Medicine, Shanghai 200032, China.
³ Clinical Research Center, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province 310009, China.
⁴ Department of Cardiology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China.

Abstract

Abdominal aortic aneurysm (AAA) is a permanent, asymptomatic segmental dilatation of the abdominal aorta, with a high mortality risk upon rupture. Identification of potential key genes and pathways may help to develop curative drugs for AAA. We conducted RNA-seq on abdominal aortic tissues from both AAA patients and normal individuals as a control group. Integrated bioinformatic analysis was subsequently performed to comprehensively reveal potential key genes and pathways. A total of 1148 differential expressed genes (DEGs) (631 up-regulated and 517 down-regulated) were identified in our study. Gene Ontology (GO) analysis revealed enrichment in terms related to extracellular matrix organization, while KEGG analysis indicated enrichment in hematopoietic cell lineage and ECM-receptor interaction. Protein-protein interaction (PPI) network analysis revealed several candidate key genes, and differential expression of 6 key genes (CXCL8, CCL2, PTGS2, SELL, CCR7, and CXCL1) was validated by Gene Expression Omnibus (GEO) datasets. Receiver operating characteristic curve (ROC) analysis demonstrated these genes' high discriminatory ability between AAA and normal tissues. Immunohistochemistry indicated that several key genes were highly expressed in AAA tissues. Single-cell RNA sequencing revealed differential distribution patterns of these identified key genes among various cell types. 26 potential drugs linked to our key genes were found through DGIdb. Overall, our study provides a comprehensive evaluation of potential key genes and pathways in AAA, which could pave the way for the development of curative pharmacological therapies.

Keywords: Abdominal aortic aneurysm; Comprehensive bioinformatics analysis; Key genes; RNA-seq analysis; ScRNA-seq analysis.