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Medicine Advances 2023, 1(3): 219-233 https://doi.org/10.1002/med4.31
Original Article | Open Access | Issue | Published: 14 September 2023

Analysis of potential key ferroptosis genes in the pathogenesis of ankylosing spondylitis by bioinformatics

Show Author's Information Guoxian He1,2,  Zexin Chen3 ( ),  Jiaxiao Li1,4,  Lanhui Zhang1,4,  Suling Liu1,  Yang Cui1,4( )
Department of Rheumatology and Immunology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
Department of Rheumatology, The People's Hospital of Gaoming District of Foshan City, Foshan, China
Department of Rheumatology and Immunology, South China Hospital of Shenzhen University, Shenzhen, China
Southern Medical University, Guangzhou, China
Keywords:
bioinformatics, ferroptosis, TLR4, ankylosing spondylitis, miR‐205‐5p, TP53
Cite this article:
He G, Chen Z, Li J, et al. Analysis of potential key ferroptosis genes in the pathogenesis of ankylosing spondylitis by bioinformatics. Medicine Advances, 2023, 1(3): 219-233. https://doi.org/10.1002/med4.31
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Abstract Full text About this article
Background

Ankylosing spondylitis (AS) is a disabling chronic inflammatory disease. Mechanisms of ferroptosis in AS remain unclear. Using bioinformatics analysis, we aimed to identify key molecules involved in ferroptosis, provide potential therapeutic targets for AS, and further explore mechanisms of ferroptosis in AS.

Methods

GSE25101 was downloaded from the Gene Expression Omnibus and intersected with a ferroptosis gene dataset. The ferroptosis‐relate differentially‐expressed genes were further subjected to functional enrichment analysis, protein interaction network analysis, and gene‐miRNA interaction network analysis, from which potential key ferroptosis genes in the pathogenesis of ankylosing spondylitis were screened.

Results

A total of 20 differentially expressed genes were screened, most of which are involved in phosphoinositide 3 kinase‐Akt or mitogen‐activated protein kinase (MAPK) signaling pathways or the endoplasmic reticulum stress response. The following target genes were identified through protein‐protein interaction network analysis and screening of key modules constructed from genes associated with PI3K‐Akt and MAPK signaling pathways: TP53, PTEN, TLR4, HSPB1, DDIT3, and XBP1. In addition, PI3K‐Akt and MAPK signaling were associated with oxidative stress, which may play a role in AS pathological ossification related to ferroptosis. Only hsa‐miR‐205‐5p was found to target at least two genes by gene‐miRNA interaction network analysis.

Conclusions

Future therapeutic drug development may intervene by modulating MAPK or PI3K‐Akt signaling pathways rather than directly affecting the interleukin 17 pathway. hsa‐miR‐205‐5p may be a potential novel biomarker for AS.


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About this article

Analysis of potential key ferroptosis genes in the pathogenesis of ankylosing spondylitis by bioinformatics

Show Author's information Guoxian He1,2, Zexin Chen3 ( ), Jiaxiao Li1,4, Lanhui Zhang1,4, Suling Liu1, Yang Cui1,4( )
Department of Rheumatology and Immunology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
Department of Rheumatology, The People's Hospital of Gaoming District of Foshan City, Foshan, China
Department of Rheumatology and Immunology, South China Hospital of Shenzhen University, Shenzhen, China
Southern Medical University, Guangzhou, China

Abstract

Background

Ankylosing spondylitis (AS) is a disabling chronic inflammatory disease. Mechanisms of ferroptosis in AS remain unclear. Using bioinformatics analysis, we aimed to identify key molecules involved in ferroptosis, provide potential therapeutic targets for AS, and further explore mechanisms of ferroptosis in AS.

Methods

GSE25101 was downloaded from the Gene Expression Omnibus and intersected with a ferroptosis gene dataset. The ferroptosis‐relate differentially‐expressed genes were further subjected to functional enrichment analysis, protein interaction network analysis, and gene‐miRNA interaction network analysis, from which potential key ferroptosis genes in the pathogenesis of ankylosing spondylitis were screened.

Results

A total of 20 differentially expressed genes were screened, most of which are involved in phosphoinositide 3 kinase‐Akt or mitogen‐activated protein kinase (MAPK) signaling pathways or the endoplasmic reticulum stress response. The following target genes were identified through protein‐protein interaction network analysis and screening of key modules constructed from genes associated with PI3K‐Akt and MAPK signaling pathways: TP53, PTEN, TLR4, HSPB1, DDIT3, and XBP1. In addition, PI3K‐Akt and MAPK signaling were associated with oxidative stress, which may play a role in AS pathological ossification related to ferroptosis. Only hsa‐miR‐205‐5p was found to target at least two genes by gene‐miRNA interaction network analysis.

Conclusions

Future therapeutic drug development may intervene by modulating MAPK or PI3K‐Akt signaling pathways rather than directly affecting the interleukin 17 pathway. hsa‐miR‐205‐5p may be a potential novel biomarker for AS.

Keywords: bioinformatics, ferroptosis, TLR4, ankylosing spondylitis, miR‐205‐5p, TP53

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Received: 26 March 2023
Accepted: 23 July 2023
Published: 14 September 2023
Issue date: September 2023

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© 2023 The Authors. Tsinghua University Press.

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ACKNOWLEDGMENTS

We thank reviewers for the comments on the content of the article, and we would like to thank all participants who participated in the study for their time and involvement.

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