RESUMEN
BACKGROUND: Osteoarthritis (OA) is a debilitating joint disorder characterized by the progressive degeneration of articular cartilage. Although the role of ion channels in OA pathogenesis is increasingly recognized, diagnostic markers and targeted therapies remain limited. METHODS: In this study, we analyzed the GSE48556 dataset to identify differentially expressed ion channel-related genes (DEGs) in OA and normal controls. We employed machine learning algorithms, least absolute shrinkage and selection operator(LASSO), and support vector machine recursive feature elimination(SVM-RFE) to select potential diagnostic markers. Then the gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) were performed to explore the potential diagnostic markers' involvement in biological pathways. Finally, weighted gene co-expression network analysis (WGCNA) was used to identify key genes associated with OA. RESULTS: We identified a total of 47 DEGs, with the majority involved in transient receptor potential (TRP) pathways. Seven genes (CHRNA4, GABRE, HTR3B, KCNG2, KCNJ2, LRRC8C, and TRPM5) were identified as the best characteristic genes for distinguishing OA from healthy samples. We performed clustering analysis and identified two distinct subtypes of OA, C1, and C2, with differential gene expression and immune cell infiltration profiles. Then we identified three key genes (PPP1R3D, ZNF101, and LOC651309) associated with OA. We constructed a prediction model using these genes and validated it using the GSE46750 dataset, demonstrating reasonable accuracy and specificity. CONCLUSIONS: Our findings provide novel insights into the role of ion channel-related genes in OA pathogenesis and offer potential diagnostic markers and therapeutic targets for the treatment of OA.
As society ages, the incidence of knee osteoarthritis continues to rise, bringing with it a series of social impacts and medical pressure. Despite the increasing recognition of the role of ion channels in the pathogenesis of OA, diagnostic markers and targeted therapies remain limited.This study investigated the role of TRP as possible diagnostic tools for OA.Seven TRP-related genes were identified as the best traits to distinguish OA from healthy samples, and then we constructed and validated risk scores for three key genes (PPP1R3D, ZNF101, and LOC651309) relevant to OA ion channel gene modules.Our findings provide novel insights into the role of ion channel-related genes in OA pathogenesis and offer a reference for further clinical diagnosis.
