Identification and validation of biomarkers FAM107A , RHOBTB1 and ZBTB16 associated with dietary restriction in osteoarthritis
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Objective
Osteoarthritis (OA), a chronic ailment that leads to joint degeneration, could be prevented by dietary restriction (DR). This study investigated the molecular mechanisms related to DR-related genes (DRRGs) as potential biomarkers in OA.
Methods
Transcriptome data of OA (GSE55235 and GSE89408) were retrieved from public databases. Differentially expressed genes (DEGs) from GSE55235 were cross-referenced with DRRGs to identify candidate genes. Machine learning techniques, expression validation, and receiver operating characteristic (ROC) curve analysis were utilized to pick out biomarkers. Functional enrichment analysis explored associated pathways, and the CIBERSORT algorithm assessed immune cell infiltration. Subsequently, an exploration was made into the associations between biomarkers and immune cells. Additionally, small-molecule compounds for treating OA were predicted and validated based on the biomarkers, and the magnitudes of biomarker expression were verified.
Results
A sum of 43 DR-related candidate genes in OA was determined. Among them, FAM107A , RHOBTB1 , and ZBTB16 were identified as biomarkers with strong predictive value for OA (AUC ≥ 0.7). Pathway enrichment analysis indicated that 3 biomarkers were significantly connected with the lysosome pathway. In terms of immune infiltration analysis, it revealed that the highest degree of positive correlation (r =0.72, P < 0.001) existed between FAM107A and CD8 T cells. Meanwhile, the most pronounced negative correlation (r=-0.74, P < 0.001) was found between RHOBTB1 and activated mast cells. Moreover, molecular docking analysis demonstrated that 4-(5-benzo(1,3) dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl) benzamide, benzo(a)pyrene, and tetrachlorodibenzodioxin had good binding affinities with the biomarkers. In addition, Reverse transcription quantitative polymerase chain reaction (RT-qPCR) confirmed that, in the OA group, the expression levels of RHOBTB1 and ZBTB16 increased, whereas the level of FAM107A was decreased ( P < 0.05).
Conclusion:
This research identified 3 DR-related biomarkers in OA, emphasizing that they were involved in the pathogenesis of OA and had the potential to serve as therapeutic targets.
