Identification of apoptosis-related key genes and the associated regulation mechanism in thoracic aortic aneurysm

Qi Ma; Long Hu; Yingwan Luo; Miao Wang; Shui Yu; Aidong Lu; Leping Zhang; Huimin Zeng

doi:10.1186/s12872-023-03516-0

Identification of apoptosis-related key genes and the associated regulation mechanism in thoracic aortic aneurysm

BMC Cardiovasc Disord. 2023 Sep 28;23(1):481. doi: 10.1186/s12872-023-03516-0.

Authors

Qi Ma^#¹, Long Hu^#², Yingwan Luo³, Miao Wang⁴, Shui Yu⁴, Aidong Lu⁴, Leping Zhang⁴, Huimin Zeng⁵

Affiliations

¹ Department of Anesthesiology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China.
² XJTLU Wisdom Lake Academy of Pharmacy, Xi'an Jiaotong-Liverpool University, Suzhou, China.
³ Department of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
⁴ Department of Pediatrics, Peking University People's Hospital, 11 Xizhimen South Street, Beijing, 100000, China.
⁵ Department of Pediatrics, Peking University People's Hospital, 11 Xizhimen South Street, Beijing, 100000, China. huiminzeng@bjmu.edu.cn.

^# Contributed equally.

Abstract

Background: This study investigated the role of apoptosis-related genes in thoracic aortic aneurysms (TAA) and provided more insights into TAA's pathogenesis and molecular mechanisms.

Material/methods: Two gene expression datasets (GSE9106 and GSE26155) were retrieved from the Gene Expression Omnibus (GEO) database. Apoptosis-related genes were obtained from the KEGG apoptosis pathway (hsa04210). Differentially expressed apoptosis-related genes were identified by performing differential expression analysis using limma for TAA blood and tissue samples. GO and KEGG enrichment analysis of the differentially expressed apoptosis genes was performed using the Metascape web tool. The miRNA-mRNA regulatory network was reconstructed using the ENCORI and miRDB databases, and functional enrichment analysis was performed on the related miRNAs using the miEAA tool. The correlation between the expression levels of differentially expressed apoptosis-related genes and genes involved in immune infiltration in TAA was calculated using the CIBERSORT algorithm. The apoptosis modification patterns mediated by differentially expressed apoptosis-related genes were systematically assessed in TAA samples.

Results: A total of 9 differentially-expressed apoptosis-related genes were identified in TAA samples compared with normal samples. 150 miRNAs and 6 mRNAs regulatory networks were reconstructed using the ENCORI and miRDB databases. Immune infiltration analysis revealed that the GZMB had the strongest positive correlation with activated NK cells and the DFFA presented the strongest positive correlation with T cells follicular helper. 3 distinct apoptosis modification patterns mediated by 9 differentially-expressed apoptosis-related genes were identified. They differ in immune characteristics and drug sensitivity, and their biological functions in these subtypes were further studied.

Conclusions: This study identified key apoptosis-related genes related to TAA and evaluated the modification patterns of key apoptosis genes in TAA, providing insights into potential targets and mechanisms of TAA pathogenesis and progression.

Keywords: Apoptosis; Bioinformatical analysis; RNA modification; Thoracic aortic aneurysm; Transcriptomics.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aortic Aneurysm, Thoracic*
Apoptosis / genetics
Gene Expression Profiling
Gene Regulatory Networks
Humans
MicroRNAs* / genetics

Substances

MicroRNAs

Grants and funding

82000151/National Natural Science Foundation of China