Application of Machine Learning and Mendelian Randomization Analysis to Identify the Cuproptosis-Related Biomarker and Its Related Regulationin Osteonecrosis of the Femoral Head

Introduction: Osteonecrosis of the Femoral Head (ONFH) is one of the common refractory diseases. However, the role of cuproptosis in ONFH pathogenesis remains unexplored. This study aimed to investigate the potential relationship between cuproptosis and ONFH. Methods: ONFH-related datasets were obtained from the Gene Expression Omnibus (GEO) database, and cuproptosis-related genes in the GSE123568 dataset were identified through differential expression analysis. To further discover potential cuproptosis-related biomarkers, Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis and Support Vector Machine (SVM) analysis were conducted. The Receiver Operating Characteristic (ROC) curve analysis was used to explore the diagnostic value of cuproptosis-related biomarkers. The summary Statisticsbased Mendelian Randomization (SMR) algorithm was used to investigate the causal relationship between the related genes and ONFH. The immune infiltration analysis was conducted to assess the effect of immune cells on ONFH. Subsequently, the GSE74089 and GSE89587 datasets were used to validate gene expression levels and predict the lncRNA-miRNA-mRNA network. Finally, quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) was employed to validate the expression of these genes. Results: The study showed that the upregulation of PDHB, a cuproptosis-related biomarker, may contribute to the development of ONFH. Additionally, immune cells were found to play a crucial role in ONFH, and PDHB showed a significant association with various immune cells. Furthermore, the study identified the existence of the MIR22HG/let-7c-5p/PDHB regulatory pathway, which may play a critical role in ONFH through cuproptosis. Discussion: This study discovered a cuproptosis-related regulating pathway, MIR22HG/let-7c- 5p/PDHB. This can provide new insights into the treatment of ONFH. However, further experimental validation is needed. result: This study showed that upregulation of the cuproptosis-related biomarker, PDHB, could lead to ONFH. At the same time, the study found that immune cells play an important role in ONFH, and PDHB is significantly associated with a variety of immune cells. The study also found the existence of MIR22HG/let-7c-5p/PDHB regulatory pathway, which may play an important role in ONFH through cuproptosis Conclusion: PDHB, identified as a cuproptosis-related biomarker, can induce ONFH through cuproptosis. PDHB also contributes to the pathogenesis and progression of ONFH by influencing immune cell function. This is most likely mediated through the regulatory interaction between MIR22HG, let-7c-5p, and PDHB.