Integrative Transcriptomic and Machine-Learning Analysis Reveals Immune-Inflammatory and Stress-Response Alterations...

Area of Science:

• Genomics and Molecular Biology
• Immunology
• Oncology

Background:

• Medication-related osteonecrosis of the jaw (MRONJ) is a severe complication of antiresorptive and antiangiogenic treatments.
• The precise molecular mechanisms underlying MRONJ are not well understood.

Purpose of the Study:

• To investigate the molecular mechanisms of MRONJ by analyzing gene expression profiles.
• To identify potential diagnostic and risk assessment biomarkers for MRONJ.

Main Methods:

• Microarray data analysis (GSE7116) of peripheral blood mononuclear cells from multiple myeloma patients with and without MRONJ, and healthy controls.
• Utilized differential gene expression analysis, gene co-expression network analysis, and machine learning algorithms (LASSO, ridge regression) for gene identification and validation.
• Functional enrichment analysis and network analysis were performed to understand the biological pathways involved.

Main Results:

• Identified distinct gene expression patterns in MRONJ patients, including upregulated ribosomal/translational pathways and suppressed neutrophil degranulation/antimicrobial defense.
• Key candidate genes (e.g., PDE4B, JAK1, ETS1) were identified with high discriminatory power (AUC 0.95-0.99).
• These genes are functionally linked to immune dysfunction, cytokine signaling, NF-κB activation, and stress response.

Conclusions:

• MRONJ is associated with a systemic immune-inflammatory imbalance and disruption of translational processes.
• The identified genes offer potential novel biomarkers for MRONJ diagnosis and risk stratification.
• Findings provide new insights into the molecular pathogenesis of MRONJ.