Molecular Subtype Classification of Postmenopausal Osteoporosis and Immune Infiltration Microenvironment Based on Bioinformatics Analysis of Osteoclast-Regulatory Genes

Osteoporosis is common in postmenopausal women but is often asymptomatic until a fracture occurs, highlighting the importance of early screening and preventive interventions. This study aimed to develop molecular subtype risk stratification of postmenopausal osteoporosis and analyze the immune infil...

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Main Authors: Yining Gong, Dingjun Hao, Yong Zhang, Yongyong Tu, Baorong He, Liang Yan
Format: Article
Language:English
Published: MDPI AG 2023-10-01
Series:Biomedicines
Subjects:
Online Access:https://www.mdpi.com/2227-9059/11/10/2701
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author Yining Gong
Dingjun Hao
Yong Zhang
Yongyong Tu
Baorong He
Liang Yan
author_facet Yining Gong
Dingjun Hao
Yong Zhang
Yongyong Tu
Baorong He
Liang Yan
author_sort Yining Gong
collection DOAJ
description Osteoporosis is common in postmenopausal women but is often asymptomatic until a fracture occurs, highlighting the importance of early screening and preventive interventions. This study aimed to develop molecular subtype risk stratification of postmenopausal osteoporosis and analyze the immune infiltration microenvironment. Microarray data for osteoporosis were downloaded and analyzed. Logistic and least absolute shrinkage and selection operator (LASSO) regression analyses were used to construct the molecular risk model. Circulating blood samples were collected from 10 enrolled participants to validate the key differentially expressed genes, and consistent clustering based on the expression profiles of candidate genes was performed to obtain molecular subtypes. Three key genes, <i>CTNNB1</i>, <i>MITF</i>, and <i>TNFSF11</i>, were obtained as variables and used to construct the risk model. External experimental validation showed substantial differences in the three key genes between patients with osteoporosis and the controls (<i>p</i> < 0.05). Three subtypes were obtained based on dimensionality reduction clustering results. Cluster 3 had significantly more patients with low bone mineral density (BMD), whereas Cluster 2 had significantly more patients with high BMD (<i>p</i> < 0.05). This study introduced a novel molecular risk model and subtype classification system, which is an evidence-based screening strategy that will guide the active prevention, early diagnosis, and treatment of osteoporosis in high-risk postmenopausal women.
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spelling doaj.art-511ac23e03614c0380b4f3a25fd0245a2023-11-19T15:45:51ZengMDPI AGBiomedicines2227-90592023-10-011110270110.3390/biomedicines11102701Molecular Subtype Classification of Postmenopausal Osteoporosis and Immune Infiltration Microenvironment Based on Bioinformatics Analysis of Osteoclast-Regulatory GenesYining Gong0Dingjun Hao1Yong Zhang2Yongyong Tu3Baorong He4Liang Yan5Department of Spine Surgery, Honghui Hospital, Xi’an Jiaotong University, Xi’an 710054, ChinaDepartment of Spine Surgery, Honghui Hospital, Xi’an Jiaotong University, Xi’an 710054, ChinaDepartment of Spine Surgery, Honghui Hospital, Xi’an Jiaotong University, Xi’an 710054, ChinaDepartment of Spine Surgery, Honghui Hospital, Xi’an Jiaotong University, Xi’an 710054, ChinaDepartment of Spine Surgery, Honghui Hospital, Xi’an Jiaotong University, Xi’an 710054, ChinaDepartment of Spine Surgery, Honghui Hospital, Xi’an Jiaotong University, Xi’an 710054, ChinaOsteoporosis is common in postmenopausal women but is often asymptomatic until a fracture occurs, highlighting the importance of early screening and preventive interventions. This study aimed to develop molecular subtype risk stratification of postmenopausal osteoporosis and analyze the immune infiltration microenvironment. Microarray data for osteoporosis were downloaded and analyzed. Logistic and least absolute shrinkage and selection operator (LASSO) regression analyses were used to construct the molecular risk model. Circulating blood samples were collected from 10 enrolled participants to validate the key differentially expressed genes, and consistent clustering based on the expression profiles of candidate genes was performed to obtain molecular subtypes. Three key genes, <i>CTNNB1</i>, <i>MITF</i>, and <i>TNFSF11</i>, were obtained as variables and used to construct the risk model. External experimental validation showed substantial differences in the three key genes between patients with osteoporosis and the controls (<i>p</i> < 0.05). Three subtypes were obtained based on dimensionality reduction clustering results. Cluster 3 had significantly more patients with low bone mineral density (BMD), whereas Cluster 2 had significantly more patients with high BMD (<i>p</i> < 0.05). This study introduced a novel molecular risk model and subtype classification system, which is an evidence-based screening strategy that will guide the active prevention, early diagnosis, and treatment of osteoporosis in high-risk postmenopausal women.https://www.mdpi.com/2227-9059/11/10/2701osteoporosismolecular subtyperisk stratificationimmune infiltration microenvironmentbioinformaticsosteoclast
spellingShingle Yining Gong
Dingjun Hao
Yong Zhang
Yongyong Tu
Baorong He
Liang Yan
Molecular Subtype Classification of Postmenopausal Osteoporosis and Immune Infiltration Microenvironment Based on Bioinformatics Analysis of Osteoclast-Regulatory Genes
Biomedicines
osteoporosis
molecular subtype
risk stratification
immune infiltration microenvironment
bioinformatics
osteoclast
title Molecular Subtype Classification of Postmenopausal Osteoporosis and Immune Infiltration Microenvironment Based on Bioinformatics Analysis of Osteoclast-Regulatory Genes
title_full Molecular Subtype Classification of Postmenopausal Osteoporosis and Immune Infiltration Microenvironment Based on Bioinformatics Analysis of Osteoclast-Regulatory Genes
title_fullStr Molecular Subtype Classification of Postmenopausal Osteoporosis and Immune Infiltration Microenvironment Based on Bioinformatics Analysis of Osteoclast-Regulatory Genes
title_full_unstemmed Molecular Subtype Classification of Postmenopausal Osteoporosis and Immune Infiltration Microenvironment Based on Bioinformatics Analysis of Osteoclast-Regulatory Genes
title_short Molecular Subtype Classification of Postmenopausal Osteoporosis and Immune Infiltration Microenvironment Based on Bioinformatics Analysis of Osteoclast-Regulatory Genes
title_sort molecular subtype classification of postmenopausal osteoporosis and immune infiltration microenvironment based on bioinformatics analysis of osteoclast regulatory genes
topic osteoporosis
molecular subtype
risk stratification
immune infiltration microenvironment
bioinformatics
osteoclast
url https://www.mdpi.com/2227-9059/11/10/2701
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AT dingjunhao molecularsubtypeclassificationofpostmenopausalosteoporosisandimmuneinfiltrationmicroenvironmentbasedonbioinformaticsanalysisofosteoclastregulatorygenes
AT yongzhang molecularsubtypeclassificationofpostmenopausalosteoporosisandimmuneinfiltrationmicroenvironmentbasedonbioinformaticsanalysisofosteoclastregulatorygenes
AT yongyongtu molecularsubtypeclassificationofpostmenopausalosteoporosisandimmuneinfiltrationmicroenvironmentbasedonbioinformaticsanalysisofosteoclastregulatorygenes
AT baoronghe molecularsubtypeclassificationofpostmenopausalosteoporosisandimmuneinfiltrationmicroenvironmentbasedonbioinformaticsanalysisofosteoclastregulatorygenes
AT liangyan molecularsubtypeclassificationofpostmenopausalosteoporosisandimmuneinfiltrationmicroenvironmentbasedonbioinformaticsanalysisofosteoclastregulatorygenes