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

Abstract Background 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. Methods The GSE123568 dataset based on peripheral blood samples from 10 healthy individuals and 30 SONFH patients was...

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Main Authors: Zhixin Wu, Yinxian Wen, Guanlan Fan, Hangyuan He, Siqi Zhou, Liaobin Chen
Format: Article
Language:English
Published: BMC 2021-01-01
Series:BMC Musculoskeletal Disorders
Subjects:
Online Access:https://doi.org/10.1186/s12891-021-03958-7
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author Zhixin Wu
Yinxian Wen
Guanlan Fan
Hangyuan He
Siqi Zhou
Liaobin Chen
author_facet Zhixin Wu
Yinxian Wen
Guanlan Fan
Hangyuan He
Siqi Zhou
Liaobin Chen
author_sort Zhixin Wu
collection DOAJ
description Abstract Background 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. Methods The 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. Results Nine 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. Conclusions Our study identified that two key genes, HEMGN and SLC2A1, might be potential diagnostic biomarkers of SONFH.
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spelling doaj.art-4a936c4f89a044dabd4f706f04b618992022-12-21T22:55:41ZengBMCBMC Musculoskeletal Disorders1471-24742021-01-0122111210.1186/s12891-021-03958-7HEMGN and SLC2A1 might be potential diagnostic biomarkers of steroid-induced osteonecrosis of femoral head: study based on WGCNA and DEGs screeningZhixin Wu0Yinxian Wen1Guanlan Fan2Hangyuan He3Siqi Zhou4Liaobin Chen5Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan UniversityDepartment of Orthopedic Surgery, Zhongnan Hospital of Wuhan UniversityDepartment of Obstetrics and Gynecology, Zhongnan Hospital of Wuhan UniversityDepartment of Orthopedic Surgery, Zhongnan Hospital of Wuhan UniversityDepartment of Orthopedic Surgery, Zhongnan Hospital of Wuhan UniversityDepartment of Orthopedic Surgery, Zhongnan Hospital of Wuhan UniversityAbstract Background 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. Methods The 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. Results Nine 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. Conclusions Our study identified that two key genes, HEMGN and SLC2A1, might be potential diagnostic biomarkers of SONFH.https://doi.org/10.1186/s12891-021-03958-7Steroid-induced osteonecrosis of the femoral headWeighted gene correlation network analysisDifferentially expressed genesDiagnostic biomarkersPeripheral blood
spellingShingle Zhixin Wu
Yinxian Wen
Guanlan Fan
Hangyuan He
Siqi Zhou
Liaobin Chen
HEMGN and SLC2A1 might be potential diagnostic biomarkers of steroid-induced osteonecrosis of femoral head: study based on WGCNA and DEGs screening
BMC Musculoskeletal Disorders
Steroid-induced osteonecrosis of the femoral head
Weighted gene correlation network analysis
Differentially expressed genes
Diagnostic biomarkers
Peripheral blood
title HEMGN and SLC2A1 might be potential diagnostic biomarkers of steroid-induced osteonecrosis of femoral head: study based on WGCNA and DEGs screening
title_full HEMGN and SLC2A1 might be potential diagnostic biomarkers of steroid-induced osteonecrosis of femoral head: study based on WGCNA and DEGs screening
title_fullStr HEMGN and SLC2A1 might be potential diagnostic biomarkers of steroid-induced osteonecrosis of femoral head: study based on WGCNA and DEGs screening
title_full_unstemmed HEMGN and SLC2A1 might be potential diagnostic biomarkers of steroid-induced osteonecrosis of femoral head: study based on WGCNA and DEGs screening
title_short HEMGN and SLC2A1 might be potential diagnostic biomarkers of steroid-induced osteonecrosis of femoral head: study based on WGCNA and DEGs screening
title_sort hemgn and slc2a1 might be potential diagnostic biomarkers of steroid induced osteonecrosis of femoral head study based on wgcna and degs screening
topic Steroid-induced osteonecrosis of the femoral head
Weighted gene correlation network analysis
Differentially expressed genes
Diagnostic biomarkers
Peripheral blood
url https://doi.org/10.1186/s12891-021-03958-7
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