https://orcid.org/0000-0001-8510-6717
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Abstract
Objective
The mechanism of ankylosing spondylitis (AS) remains unclear, and clinical diagnosis still pose challenges. This study aims to explore potential regulatory mechanisms underlying AS and develop a novel diagnostic model.
Methods
Interspinous ligament (ISL) tissues were collected from control samples and ankylosing spondylitis with kyphotic deformity (AS-KD) samples during surgery, followed by high-throughput sequencing. By integrating gene expression profiles from publicly available AS peripheral blood (PB) samples, differentially expressed immune genes (DEIRGs) were identified. Through gene set enrichment analysis(GSEA), gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, the regulatory mechanisms of the immune gene family in AS were explored. A diagnostic model for AS were constructed and validated it externally. Additionally, a competing endogenous RNA(ceRNA)-protein regulatory network was built for key immune genes.
Results
Adrenergic receptor beta 2 (ADRB2) was downregulated in both ISL and PB samples. It was enriched in common pathways, including natural killer cell-mediated cytotoxicity, B cell receptor signaling pathway, Th1 and Th2 cell differentiation. Using the LASSO algorithm, 12 DEIRGs were identified, including the downregulated ADRB2. Based on the DEIRGs family, a novel diagnostic model was constructed with an AUC of 0.87 for the validation set and 0.7 for the test set. The AUC for ADRB2 alone was 0.75. Subgrouping AS based on these immune genes revealed a close association with neutrophils. GSEA and KEGG analysis of ISL, PB, and subgrouping of AS showed that ADRB2 may be involved in regulating the T cell receptor signaling pathway. Immune infiltration analysis indicated a decrease in CD8+ T cell infiltration, which was positively correlated with ADRB2. ADRB2 in AS-KD was regulated by multiple ceRNA-protein (lncRNA-[hsa-miR-513a-5p]-mRNA-protein).
Conclusion
The immune gene family, especially ADRB2, participates in the mechanism and contributes to the diagnosis of AS.
Data Sharing Statement
All data that support the findings of this study are included in this manuscript and its Supplementary Information Files. Further enquiries can be directed to the corresponding author.
Institutional Review Board Statement
The study was carried out in accordance with the Declaration of Helsinki statement. The present study was approved by the Ethics Committee of Guangxi Medical University Cancer Hospital. The need for written informed consent was waived by Guangxi Medical University Cancer Hospital Ethical Review Committee due to the retrospective nature of the study. Written informed consent was not obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.
Acknowledgments
We thank all the patients who participated in this study. We thank all reviewers for their time and thoughtful critiques to refine our manuscript. Additionally, we would like to extend our appreciation to the research teams who have made the gene sets readily available in the NCBI GEO database (https://www.ncbi.nlm.nih.gov/geo/).
Author Contributions
All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.
Disclosure
All authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.