Integrative gene expression analysis and animal model reveal immune‐ and autophagy‐related biomarkers in osteomyelitis

Author:

Shi Xiangwen123,Li Mingjun23,Ni Haonan4,Wu Yipeng123,Li Yang23,Chen Xianjun5,Xu Yongqing23ORCID

Affiliation:

1. Kunming Medical University Kunming China

2. Laboratory of Yunnan Traumatology and Orthopedics Clinical Medical Center Yunnan Orthopedics and Sports Rehabilitation Clinical Medical Research Center Kunming China

3. Department of Orthopedic Surgery 920th Hospital of Joint Logistics Support Force of PLA Kunming Yunnan China

4. Orthopedic Department First People's Hospital of Huzhou, First Affiliated Hospital of Huzhou University Huzhou China

5. Department of Neurosurgery Nanping First Hospital Affiliated to Fujian Medical University Nanping Fujian China

Abstract

AbstractBackgroundOsteomyelitis (OM) is recognized as a significant challenge in orthopedics due to its complex immune and inflammatory responses. The prognosis heavily depends on timely diagnosis, accurate classification, and assessment of severity. Thus, the identification of diagnostic and classification‐related genes from an immunological standpoint is crucial for the early detection and tailored treatment of OM.MethodsTranscriptomic data for OM was sourced from the Gene Expression Omnibus (GEO) database, leading to the identification of autophagy‐ and immune‐related differentially expressed genes (AIR‐DEGs) through differential expression analysis. Diagnostic and classification models were subsequently developed. The CIBERSORT algorithm was utilized to examine immune cell infiltration in OM, and the relationship between OM clusters and various immune cells was explored. Key AIR‐DEGs were further validated through the creation of OM animal models.ResultsAnalysis of the transcriptomic data revealed three AIR‐DEGs that played a significant role in immune responses and pathways. Nomogram and receiver operating characteristic curve analyses were performed, demonstrating excellent diagnostic capability for differentiating between OM patients and healthy individuals, with an area under the curve of 0.814. An unsupervised clustering analysis discerned two unique patterns of autophagy‐ and immune‐related genes, as well as gene patterns. Further exploration into immune infiltration exhibited notable variances across different subtypes, especially between OM cluster 1 and gene cluster A, highlighting their potential role in mitigating inflammatory responses by regulating immune activities. Moreover, the mRNA and protein expression levels of three AIR‐DEGs in the animal model were aligned with those in the training and validation data sets.ConclusionsFrom an immunological perspective, a diagnostic model was successfully developed, and two distinct clustering patterns were identified. These contributions offer a significant resource for the early detection and personalized immunotherapy of patients with OM.

Publisher

Wiley

Reference53 articles.

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4. Staphylococcus aureus Osteomyelitis: Bone, Bugs, and Surgery

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