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

Abstract

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 Statistics-based 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 , 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 // 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.

Conclusion

, identified as a cuproptosis-related biomarker, can induce ONFH through cuproptosis. also contributes to the pathogenesis and progression of ONFH by influencing immune cell function. This is most likely mediated through the regulatory interaction between and .

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2025-10-23
2025-12-04

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/content/journals/cg/10.2174/0113892029373131251017114954
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Application of Machine Learning and Mendelian Randomization Analysis to Identify the Cuproptosis-Related Biomarker and Its Related Regulation in Osteonecrosis of the Femoral Head
Bentham Science Publishers ; https://doi.org/10.2174/0113892029373131251017114954
/content/journals/cg/10.2174/0113892029373131251017114954
/content/journals/cg/10.2174/0113892029373131251017114954
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  • Article Type:     Research Article
Keywords: biomarker ; immune infiltration ; machine learning ; SMR ; Osteonecrosis of the femoral head ; cuproptosis

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