Screening of Potential Biomarkers in the Peripheral Serum for Steroid-Induced Osteonecrosis of the Femoral Head Based on WGCNA and Machine Learning Algorithms

Jian Zhang,Jianyu Liu,Weiguang Xin,Chi Huang,Zilong Shen,Shuai Ren,Kecheng Han,Zehan Liu,Guanyi He,Fu Wang

doi:10.1155/2022/2639470

Abstract

Background Steroid-induced osteonecrosis of the femoral head (SONFH) has produced a substantial burden of medical and social experience. However, the current diagnosis is still limited. Thus, this study is aimed at identifying potential biomarkers in the peripheral serum of patients with SONFH. Methods The expression profile data of SONFH (number: GSE123568) was acquired from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) in SONFH were identified and used for weighted gene coexpression network analysis (WGCNA). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to investigate the biological functions. The protein-protein interaction (PPI) network and machine learning algorithms were employed to screen for potential biomarkers. Gene set enrichment analysis (GSEA), transcription factor (TF) enrichment analysis, and competing endogenous RNA (ceRNA) network were used to determine the biological functions and regulatory mechanisms of the potential biomarkers. Results A total of 562 DEGs, including 318 upregulated and 244 downregulated genes, were identified between SONFH and control samples, and 94 target genes were screened based on WGCNA. Moreover, biological function analysis suggested that target genes were mainly involved in erythrocyte differentiation, homeostasis and development, and myeloid cell homeostasis and development. Furthermore, GYPA, TMCC2, and BPGM were identified as potential biomarkers in the peripheral serum of patients with SONFH based on machine learning algorithms and showed good diagnostic values. GSEA revealed that GYPA, TMCC2, and BPGM were mainly involved in immune-related biological processes (BPs) and signaling pathways. Finally, we found that GYPA might be regulated by hsa-miR-3137 and that BPGM might be regulated by hsa-miR-340-3p. Conclusion GYPA, TMCC2, and BPGM are potential biomarkers in the peripheral serum of patients with SONFH and might affect SONFH by regulating erythrocytes and immunity.

Highlights

Steroid-induced osteonecrosis of the femoral head (SONFH), a chronic and progressive femoral head disease mainly induced by long-term exposure to excessive glucocorticoids, can cause hip joint damage and dysfunction and affect the quality of life [1]
To further screen genes related to SONFH, weighted gene coexpression network analysis (WGCNA) was performed using 562 Differentially expressed genes (DEGs)
We explored the regulatory mechanisms of GYPA, TMCC2, and BPGM and found that GYPA might be regulated by hsa-miR-3137, and BPGM might be regulated by hsa-miR-340-3p

Summary

Introduction

Steroid-induced osteonecrosis of the femoral head (SONFH), a chronic and progressive femoral head disease mainly induced by long-term exposure to excessive glucocorticoids, can cause hip joint damage and dysfunction and affect the quality of life [1]. The diagnosis of SONFH, especially joint imaging techniques, is well established, patients with an early stage of SONFH are difficult to find because of the lack of effective and specific biomarkers [4]. This study is aimed at identifying potential biomarkers in the peripheral serum of patients with SONFH. A total of 562 DEGs, including 318 upregulated and 244 downregulated genes, were identified between SONFH and control samples, and 94 target genes were screened based on WGCNA. GYPA, TMCC2, and BPGM were identified as potential biomarkers in the peripheral serum of patients with SONFH based on machine learning algorithms and showed good diagnostic values. GYPA, TMCC2, and BPGM are potential biomarkers in the peripheral serum of patients with SONFH and might affect SONFH by regulating erythrocytes and immunity

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