Revealing the impact of TOX3 on osteoarthritis: insights from bioinformatics

Abstract

Osteoarthritis, a prevalent long-term condition of the joints, primarily impacts older individuals, resulting in discomfort, restrictions in mobility, and a decrease in overall well-being. Although Osteoarthritis is widely spread, there is a lack of successful interventions to stop the advancement of the condition. Numerous signaling pathways have been emphasized in recent research on Osteoarthritis, yet the diagnostic significance of numerous genes has not been investigated. To identify genes that were expressed differently in osteoarthritis, we utilized the Gene Expression Omnibus database. To identify marker genes, we built machine learning models including Least Absolute Shrinkage and Selection Operator and Random Forest. We categorized Osteoarthritis samples and performed immune cell infiltration analysis based on the expression patterns of these characteristic genes. Both the Least Absolute Shrinkage and Selection Operator and Random Forest models selected six marker genes (TOX3, ARG1, CST7, RERGL, COL11A1, NCRNA00185) out of a total of 17 differentially expressed genes. The osteoarthritis samples were categorized into two groups, namely a high expression group and a low expression group, based on the median levels of TOX3 expression. Comparative analysis of these groups identified 85 differentially expressed genes, showing notable enrichment in pathways related to lipid metabolism in the group with high expression. Analysis of immune cell infiltration revealed noticeable differences in immune profiles among the two groups. The group with high expression of TOX3 showed a notable increase in Mast cells and Type II IFN Response, whereas B cells, Cytolytic activity, Inflammation-promoting cells, NK cells, pDCs, T cell co-inhibition, Th1 cells, and Th2 cells were significantly decreased. We constructed a ceRNA network for TOX3, revealing 57 lncRNAs and 18 miRNAs involved in 57 lncRNA-miRNA interactions, and 18 miRNA-mRNA interactions with TOX3. Validation of TOX3 expression was confirmed using an external dataset (GSE29746), revealing a notable increase in Osteoarthritis samples. In conclusion, our study presents a comprehensive analysis identifying TOX3 as a potential feature gene in Osteoarthritis. The distinct immune profiles and involvement in fat metabolism pathways associated with TOX3 expression suggest its significance in Osteoarthritis pathogenesis. The study establishes a basis for comprehending the intricate correlation between characteristic genes and Osteoarthritis, as well as for the formulation of individualized therapeutic approaches.

Keywords: TOX high mobility group box family member 3; ceRNA network; immune infiltration analysis; machine learning models; osteoarthritis.