激素性股骨头坏死免疫诊断标志物的鉴定与药物筛选
Identification of immunodiagnostic biomarkers and drug screening for steroid-induced osteonecrosis of the femoral head
摘要
Abstract
BACKGROUND:The pathogenesis of steroid-induced osteonecrosis of the femoral head is not yet fully understood.A deep comprehension of the pathology and molecular mechanisms of steroid-induced osteonecrosis of the femoral head,as well as the search for diagnostic markers with high specificity and sensitivity,are crucial for the prevention and treatment of this condition. OBJECTIVE:To identify immune diagnostic markers for steroid-induced osteonecrosis of the femoral head and predict potential drug targets through drug enrichment analysis and molecular docking techniques. METHODS:The study utilized gene expression profile data(GSE123568 and GSE74089)from the GEO databases(a public gene expression database built by the U.S.National Center for Biotechnology Information).R software was used for data normalization and differential gene screening,followed by weighted gene co-expression network analysis(WGCNA)to identify disease-related genes.Immune-related genes were obtained from the GeneCards database and intersected with the differential genes and WGCNA gene sets to select immune-related genes for steroid-induced osteonecrosis of the femoral head.Mendelian randomization was used to validate the potential causal relationship between these immune-related genes and steroid-induced osteonecrosis of the femoral head.Gene Set Enrichment Analysis was conducted to analyze the immune-related pathways involved,and protein-protein interaction networks were used to assess functional associations.Finally,drug enrichment analysis and molecular docking were performed to predict potential drugs targeting these immune-related genes. RESULTS AND CONCLUSION:Three key immune-related genes-RNASEL,SECTM1,and HSPA6-were identified.These genes were highly expressed in steroid-induced osteonecrosis of the femoral head and exhibited good diagnostic potential,which were involved in multiple immune-related signaling pathways.Mendelian randomization analysis confirmed their potential causal relationship with steroid-induced osteonecrosis of the femoral head.Drug enrichment analysis and molecular docking identified nine potential drugs,including β-ecdysterone,showing the possibility of intervening in the pathological process of steroid-induced osteonecrosis of the femoral head by regulating the HSPA6 protein.These findings provide new biomarkers and drug targets for the early diagnosis and personalized treatment of steroid-induced osteonecrosis of the femoral head.They also highlight the potential application of bioinformatics in Chinese biomedical research,facilitating the integration and translational use of international data in local disease studies.关键词
生物信息学分析/孟德尔随机化/免疫相关基因/激素性股骨头坏死/加权基因共表达网络分析/工程化组织构建Key words
bioinformatics analysis/Mendelian randomization/immune-related genes/steroid-induced osteonecrosis of the femoral head/weighted correlation network analysis/engineered tissue construction分类
医药卫生引用本文复制引用
韩杰,潘成镇,尚昱志,张驰..激素性股骨头坏死免疫诊断标志物的鉴定与药物筛选[J].中国组织工程研究,2025,29(35):7690-7700,11.基金项目
国家自然科学基金项目(82260858,82460872),项目负责人:韩杰 （82260858,82460872）
广西自然科学基金项目(2024GXNSFAA010243),项目负责人:韩杰 （2024GXNSFAA010243）
广西高水平中医药重点学科建设试点项目(桂中医药科教发[2023]13号),项目负责人:韩杰 （桂中医药科教发[2023]13号）
广西中医药重点研究室建设项目(桂中医药科教发[2023]9号),项目负责人:韩杰 （桂中医药科教发[2023]9号）
广西青年岐黄学者培养项目(桂中医药科教发[2022]13号),项目负责人:韩杰 （桂中医药科教发[2022]13号）
广西中医药大学"岐黄工程"高层次人才团队培育项目(桂中医大党[2024]3号),项目负责人:韩杰 National Natural Science Foundation of China,Nos.82260858 and 82460872(to HJ) （桂中医大党[2024]3号）
Guangxi Natural Science Foundation,No.2024GXNSFAA010243(to HJ) （to HJ）
Pilot Project for the High-Level Construction of Key Disciplines of Chinese Medicine in Guangxi,No.[2023]13(to HJ) （to HJ）
Guangxi Key Research Laboratory Construction Project of Traditional Chinese Medicine,No.[2023]9(to HJ) （to HJ）
Guangxi Young Qihuang Scholars Training Project,No.[2022]13(to HJ) （to HJ）
"Qihuang Engineering"High-Level Talent Team Cultivation Project of Guangxi University of Chinese Medicine,No.[2024]3(to HJ) （to HJ）
