Exploring Endoplasmic Reticulum Stress-Related Genes in Cartilage Defects: Implications for Diagnosis and Therapy

Area of Science:

• Orthopedics
• Biomolecular mechanisms
• Computational biology

Background:

• Cartilage defects (CDs) present a significant clinical challenge due to their limited regenerative capacity.
• Early and accurate detection of CDs is crucial for effective management and treatment strategies.

Purpose of the Study:

• To identify novel endoplasmic reticulum (ER) stress-related biomarkers for cartilage defects (CDs).
• To develop a diagnostic model for enhancing the early detection of CDs.
• To investigate the interplay between ER stress and immune dysregulation in CD pathogenesis.

Main Methods:

• Transcriptomic data analysis (GSE129147) to identify ER stress-related differentially expressed genes (ERSRDEGs).
• Functional enrichment analysis using Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO).
• Assessment of immune infiltration and construction of diagnostic models using logistic regression, support vector machine, and LASSO regression.

Main Results:

• Twenty ERSRDEGs were identified, with CYBB, ATP6V1A, and TNFRSF12A significantly upregulated in CD tissues.
• Functional analyses implicated oxidative stress response and extracellular matrix remodeling in CD pathogenesis.
• A preliminary diagnostic model incorporating TNFRSF12A, TWIST1, and ATP6V1A demonstrated good predictive accuracy (AUC: 0.7-0.9).

Conclusions:

• Endoplasmic reticulum (ER) stress and immune imbalance are key contributors to cartilage degeneration in CDs.
• The identified genes, particularly TNFRSF12A, TWIST1, and ATP6V1A, represent potential biomarkers for CD.
• The developed ERSRDEG-based diagnostic model offers preliminary bioinformatics evidence for targeted diagnostics and therapies in CDs.