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

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 f...

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Autores principales: Wu, Zhixin, Wen, Yinxian, Fan, Guanlan, He, Hangyuan, Zhou, Siqi, Chen, Liaobin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7811219/
https://www.ncbi.nlm.nih.gov/pubmed/33451334
http://dx.doi.org/10.1186/s12891-021-03958-7
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author Wu, Zhixin
Wen, Yinxian
Fan, Guanlan
He, Hangyuan
Zhou, Siqi
Chen, Liaobin
author_facet Wu, Zhixin
Wen, Yinxian
Fan, Guanlan
He, Hangyuan
Zhou, Siqi
Chen, Liaobin
author_sort Wu, Zhixin
collection PubMed
description 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12891-021-03958-7.
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spelling pubmed-78112192021-01-18 HEMGN and SLC2A1 might be potential diagnostic biomarkers of steroid-induced osteonecrosis of femoral head: study based on WGCNA and DEGs screening Wu, Zhixin Wen, Yinxian Fan, Guanlan He, Hangyuan Zhou, Siqi Chen, Liaobin BMC Musculoskelet Disord Research Article 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12891-021-03958-7. BioMed Central 2021-01-15 /pmc/articles/PMC7811219/ /pubmed/33451334 http://dx.doi.org/10.1186/s12891-021-03958-7 Text en © The Author(s) 2021 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Article
Wu, Zhixin
Wen, Yinxian
Fan, Guanlan
He, Hangyuan
Zhou, Siqi
Chen, Liaobin
HEMGN and SLC2A1 might be potential diagnostic biomarkers of steroid-induced osteonecrosis of femoral head: study based on WGCNA and DEGs screening
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 Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7811219/
https://www.ncbi.nlm.nih.gov/pubmed/33451334
http://dx.doi.org/10.1186/s12891-021-03958-7
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