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Identification of Potential Core Genes in Medication-Related Osteonecrosis of the Jaw via Bioinformatics Analysis
Xinliang Duan1,2, Yifu Bian1,2, Sichen Han1,2
1Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Jilin University, Changchun, China.
Background:
Medication-related osteonecrosis of the jaw (MRONJ) is a severe complication associated with antiresorptive or antiangiogenic therapy, yet its molecular mechanisms remain poorly understood. This study aimed to identify potential core genes involved in MRONJ pathogenesis through integrative bioinformatics analysis.
Methods:
GSE7116 dataset (PBMC samples from 11 MRONJ and 10 non-MRONJ multiple myeloma patients on bisphosphonates) was analyzed. DEGs were identified using GEO2R. Functional enrichment, PPI network, hub gene identification, ROC-based diagnostic evaluation, and independent qRT-PCR validation were performed.
Results:
241 DEGs (212 down, 29 up) were identified, enriched in immune/inflammatory responses and NOD-like receptor/NF-κB pathways. Ten hub genes (TNF, ACTB, IL1B, JUN, CXCL8, CXCR4, PTPRC, IL1A, HSP90AB1, RHOA) were identified. Four of them (HSP90AB1, RHOA, CXCL8, IL1B) showed high diagnostic accuracy (AUC 0.864-0.936) and were validated by qRT-PCR.
Conclusion:
This integrative bioinformatics analysis, combined with ROC evaluation and experimental qPCR validation, identifies immune- and inflammation-related hub genes as central to MRONJ pathogenesis. A four-gene signature (HSP90AB1, RHOA, CXCL8, IL1B) shows high diagnostic accuracy (AUC 0.864-0.936) and is proposed as a peripheral blood-based diagnostic panel. The widespread downregulation of inflammatory genes in PBMCs suggests systemic immunosuppression rather than overt inflammation, offering new insights for immunomodulatory strategies.
Insights
This study identifies key immune and inflammation genes linked to medication-related osteonecrosis of the jaw (MRONJ). A four-gene signature in peripheral blood shows high accuracy for diagnosing MRONJ.
Area of Science:
- Biomedical research
- Bioinformatics
- Genomics
Background:
- Medication-related osteonecrosis of the jaw (MRONJ) is a serious complication of antiresorptive/antiangiogenic therapies.
- The molecular mechanisms underlying MRONJ remain poorly understood, hindering effective treatment strategies.
Purpose of the Study:
- To identify core genes involved in MRONJ pathogenesis using integrative bioinformatics.
- To explore potential diagnostic biomarkers for MRONJ in peripheral blood.
Main Methods:
- Analysis of gene expression data from patients with and without MRONJ.
- Identification of differentially expressed genes (DEGs) and pathway enrichment analysis.
- Construction of protein-protein interaction (PPI) networks, hub gene identification, and diagnostic evaluation using ROC analysis, followed by qRT-PCR validation.
Main Results:
- 241 DEGs were identified, primarily enriched in immune/inflammatory pathways (NOD-like receptor/NF-κB).
- Ten hub genes were identified, with four (HSP90AB1, RHOA, CXCL8, IL1B) demonstrating high diagnostic accuracy (AUC 0.864-0.936).
- These four genes were validated by qRT-PCR, confirming their role in MRONJ.
Conclusions:
- Integrative bioinformatics and validation reveal immune- and inflammation-related hub genes are central to MRONJ.
- A four-gene signature (HSP90AB1, RHOA, CXCL8, IL1B) offers a promising peripheral blood-based diagnostic panel for MRONJ.
- Downregulation of inflammatory genes suggests systemic immunosuppression in MRONJ, opening avenues for immunomodulatory therapies.
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