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

Galina Laputková1, Ivan Talian1, Ján Sabo1

  • 1Department of Medical and Clinical Biophysics, Faculty of Medicine, Pavol Jozef Šafárik University, 040 11 Košice, Slovakia.

International Journal of Molecular Sciences
|December 30, 2025
PubMed
Summary
This summary is machine-generated.

Medication-related osteonecrosis of the jaw (MRONJ) involves altered gene expression, particularly in ribosomal and immune pathways. This study identifies key genes that could aid in diagnosing and assessing the risk of MRONJ.

Keywords:
MRONJWGCNAbiomarkersimmune dysregulationstress responsetranscriptomics

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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.