HEMGN and SLC2A1 might be potential diagnostic biomarkers of steroid-induced osteonecrosis of femoral head: study based on WGCNA and DEGs screening

Hangyuan He,Liaobin Chen,Yinxian Wen,Siqi Zhou,Zhixin Wu,Guanlan Fan

doi:10.1186/s12891-021-03958-7

Abstract

BackgroundSteroid-induced osteonecrosis of the femoral head (SONFH) is a chronic and crippling bone disease. This study aims to reveal novel diagnostic biomarkers of SONFH.MethodsThe GSE123568 dataset based on peripheral blood samples from 10 healthy individuals and 30 SONFH patients was used for weighted gene co-expression network analysis (WGCNA) and differentially expressed genes (DEGs) screening. The genes in the module related to SONFH and the DEGs were extracted for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Genes with |gene significance| > 0.7 and |module membership| > 0.8 were selected as hub genes in modules. The DEGs with the degree of connectivity ≥5 were chosen as hub genes in DEGs. Subsequently, the overlapping genes of hub genes in modules and hub genes in DEGs were selected as key genes for SONFH. And then, the key genes were verified in another dataset, and the diagnostic value of key genes was evaluated by receiver operating characteristic (ROC) curve.ResultsNine gene co-expression modules were constructed via WGCNA. The brown module with 1258 genes was most significantly correlated with SONFH and was identified as the key module for SONFH. The results of functional enrichment analysis showed that the genes in the key module were mainly enriched in the inflammatory response, apoptotic process and osteoclast differentiation. A total of 91 genes were identified as hub genes in the key module. Besides, 145 DEGs were identified by DEGs screening and 26 genes were identified as hub genes of DEGs. Overlapping genes of hub genes in the key module and hub genes in DEGs, including RHAG, RNF14, HEMGN, and SLC2A1, were further selected as key genes for SONFH. The diagnostic value of these key genes for SONFH was confirmed by ROC curve. The validation results of these key genes in GSE26316 dataset showed that only HEMGN and SLC2A1 were downregulated in the SONFH group, suggesting that they were more likely to be diagnostic biomarkers of SOFNH than RHAG and RNF14.ConclusionsOur study identified that two key genes, HEMGN and SLC2A1, might be potential diagnostic biomarkers of SONFH.

Highlights

Steroid-induced osteonecrosis of the femoral head (SONFH) is a chronic and crippling bone disease
Our study identified that two key genes, HEMGN and SLC2A1, might be potential diagnostic biomarkers of SONFH
There are approximately 10,000 to 20,000 new non-traumatic osteonecrosis of the femoral head (NONFH) cases reported each year in the United States alone, while the estimated NONFH cases in China were 8.12 million in the population aged 15 years and over, among which SONFH counted for 47.4% of the total NONFH cases [2,3,4]

Summary

Introduction

Steroid-induced osteonecrosis of the femoral head (SONFH) is a chronic and crippling bone disease. This study aims to reveal novel diagnostic biomarkers of SONFH. Steroid-induced osteonecrosis of the femoral head (SONFH) is a chronic and crippling disease of the femoral head, due to the disruption of the blood supply of the femoral head and the subsequent death of bone cells after chronic exposure to excessive glucocorticoids, which results in the collapse of the femoral head and dysfunction of the hip joint [1]. Many studies have identified the biomarkers of diseases by screening differentially expressed genes (DEGs). WGCNA has been widely used to identify the hub genes related to clinical features in different diseases, such as osteoarthritis [7], acute myocardial infarction [8], bladder cancer [9] and pancreatic cancer [10]

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