Bioinformatics Analysis of the Molecular Mechanism and Potential Treatment Target of Ankylosing Spondylitis

Meng, Fanyan; Du, Ningna; Li, Kuai; Liu, Lanying; Xiu, Minning

doi:10.1155/2021/7471291

Cited by 6 publications

(3 citation statements)

References 39 publications

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“…Many studies have observed the important role of MRPL13 in the development and prognosis of various cancers such as breast cancer and AS. [ 16 , 20 , 21 ] In summary, the present study provides new evidence for the transcriptomic association between AS and MDD.…”

Section: Discussionmentioning

confidence: 56%

Genetic association between ankylosing spondylitis and major depressive disorders: Shared pathways, protein networks and the key gene

Dong

Lü

et al. 2023

Medicine

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The prevalence of ankylosing spondylitis (AS) and major depressive disorders (MDD) becomes increasingly pronounced, exerting a significant impact on the life quality of contemporary people. Although there is mounting evidence of a link between AS and major depression disorders, the specific interactions between the two have not been thoroughly investigated. To this end, this study aimed to check whether the gene expression profiles of patients with AS and major depression disorders overlapped, and whether there were any functional links between the identified genes via protein-protein interactions. Herein, the relationship between the 4 datasets (GSE73754, GSE98793, GSE25101, and GSE54564) chosen from the Gene Expression Omnibus for evaluation and validation was investigated using gene characterization and functional enrichment. Then, following Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes that explore the biological processes of common genes and demonstrate the interrelationships between common genes, hub genes were obtained using the STRING database and the application cytoHubba plugin of Cytoscape software. The correlation between the gene and 22 types of immuno-infiltrating cells was explored, and the key gene as well as the diagnostic efficiency of the key gene was obtained through verification. A total of 204 shared genes were discovered, the majority of which were functionally enriched in Ribosome, Coronavirus disease COVID19, Starch and sucrose metabolism, and Galactose metabolism. Then, efforts were made to go through STRING. Immuno-infiltration studies revealed that Neutrophils, T cells CD8, T cells CD4 naive, T cells CD4 memory resting, T cells CD4 memory activated, and T cells regulatory were associated with the pathogenesis of AS and MDD. Additionally, the receiver operating characteristic curve revealed that the key gene MRPL13 played diagnostic roles in AS and MDD after intersecting 10 hub genes with 37 differential expression genes from the 2 validation datasets. The obtained results suggest an overlapping genetic structure between AS and major depression disorders. MRPL13 may provide key insights into the relationship between AS and MDD.

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Section: Discussionmentioning

confidence: 56%

Genetic association between ankylosing spondylitis and major depressive disorders: Shared pathways, protein networks and the key gene

Dong

Lü

et al. 2023

Medicine

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“…In previous bioinformatics studies, researchers have mainly analyzed a single disease. Meng et al [ 35 ] found the hub genes, comprising MRPL13, MRPL22, LSM3, COX7A2, COX7C, EP300, PTPRC, and CD4, which could be the treatment targets in AS. Cheng et al [ 36 ] found that GNG11, GNB4, AGT, PIK3R3, and CCR7 are key genes that have the significance of distinguishing biomarkers in IBD disease.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics Analysis of Immune Cell Infiltration and Diagnostic Biomarkers between Ankylosing Spondylitis and Inflammatory Bowel Disease

Zhang

Chen

Qian

et al. 2023

Computational and Mathematical Methods in Medicine

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Background. Ankylosing spondylitis (AS) and inflammatory bowel disease (IBD) are both autoimmune diseases, and they often occur together in clinical practice, but the pathogenesis is unclear. This study is aimed at identifying the hub genes and explore the related immune molecular mechanisms between AS and IBD by bioinformatics analysis. Methods. From the public Gene Expression Omnibus (GEO) database, the AS and IBD datasets (GSE73754, GSE59071, GSE25101, and GSE36807) were obtained. The immune cell infiltration in the peripheral blood tissues of GSE73754 and GSE59071 was assessed using the CIBERSORT algorithm. Then, we used the Weighted Gene Coexpression Network Analysis (WGCNA) to identify the Differentially Expressed Genes (DEGs) related to AS and IBD. Then, the immune genes from the ImmPort database intersected with the DEGs to obtain hub genes. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyzed the functional correlation of hub genes. Then, hub genes were verified in GSE25101 and GSE36807. The clusterProfiler software and Gene Set Enrichment Analysis (GSEA) were used to conduct functional enrichment and pathway enrichment studies. Finally, the diagnostic efficacy was assessed using Receiver Operating Characteristic (ROC) curve analysis. Results. The analysis of immune characteristics showed that both AS and IBD were related to immunity, and neutrophils were positively correlated in both diseases. Nine coexpressed genes, including FCGRT, S100A11, IFNGR1, NFKBIZ, JAK2, LYN, PLAUR, ADM, and IL1RN, were linked to immune cells. The GO and KEGG analyses results showed that enrichment analysis was mainly related to cell transport and migration. Finally, the ROC curve was verified with the validation set, and it was found that PLAUR has clinical diagnostic significance and the most excellent specificity and sensitivity, respectively. Conclusions. PLAUR (uPAR) is a promising biomarker and will be an underlying genetic biomarker for diagnosing AS comorbid IBD. Inflammation and immunological modulation mediated by neutrophil infiltration were important in the development of AS and IBD and may be diagnostic and therapeutic targets.

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“…That study also showed that the ferroptosis pathway is a significantly enriched term through a gene set enrichment analysis of KEGG pathways. Meng et al performed a comparative bioinformatics analysis in 16 AS patients and 16 matched controls using the dataset GSE25101, and found that ferroptosis is one of the significantly enriched terms in the KEGG analysis of upregulated DEGs [ 60 ]. Based on this evidence, we used computational methods to further investigate the molecular mechanisms connecting ferroptosis and AS in order to provide a basis for future etiological studies on AS, and aid in the development of new therapeutic targets for AS patients.…”

Section: Discussionmentioning

confidence: 99%

New Insights into the Regulatory Role of Ferroptosis in Ankylosing Spondylitis via Consensus Clustering of Ferroptosis-Related Genes and Weighted Gene Co-Expression Network Analysis

Rong

Jia

et al. 2022

Genes

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The pathogenesis of ankylosing spondylitis (AS) remains undetermined. Ferroptosis is a newly discovered form of regulated cell death involved in multiple autoimmune diseases. Currently, there are no reports on the connection between ferroptosis and AS. Methods: AS samples from the Gene Expression Omnibus were divided into two subgroups using consensus clustering of ferroptosis-related genes (FRGs). Weighted gene co-expression network analysis (WGCNA) of the intergroup differentially expressed genes (DEGs) and protein–protein interaction (PPI) analysis of the key module were used to screen out hub genes. A multifactor regulatory network was then constructed based on hub genes. Results: The 52 AS patients in dataset GSE73754 were divided into cluster 1 (n = 24) and cluster 2 (n = 28). DEGs were mainly enriched in pathways related to mitochondria, ubiquitin, and neurodegeneration. Candidate hub genes, screened by PPI and WGCNA, were intersected. Subsequently, 12 overlapping genes were identified as definitive hub genes. A multifactor interaction network with 45 nodes and 150 edges was generated, comprising the 12 hub genes and 32 non-coding RNAs. Conclusions: AS can be divided into two subtypes according to FRG expression. Ferroptosis might play a regulatory role in AS. Tailoring treatment according to the ferroptosis status of AS patients can be a promising direction.

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Bioinformatics Analysis of the Molecular Mechanism and Potential Treatment Target of Ankylosing Spondylitis

Cited by 6 publications

References 39 publications

Genetic association between ankylosing spondylitis and major depressive disorders: Shared pathways, protein networks and the key gene

Genetic association between ankylosing spondylitis and major depressive disorders: Shared pathways, protein networks and the key gene

Bioinformatics Analysis of Immune Cell Infiltration and Diagnostic Biomarkers between Ankylosing Spondylitis and Inflammatory Bowel Disease

New Insights into the Regulatory Role of Ferroptosis in Ankylosing Spondylitis via Consensus Clustering of Ferroptosis-Related Genes and Weighted Gene Co-Expression Network Analysis

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