中国组织工程研究

中国组织工程研究 ›› 2025, Vol. 29 ›› Issue (35): 7690-7700.doi: 10.12307/2025.973

• 组织构建相关数据分析 Date analysis of organization construction • 上一篇    

激素性股骨头坏死免疫诊断标志物的鉴定与药物筛选

韩  杰1，潘成镇2，尚昱志1，张  驰1   

  1. 1广西中医药大学附属瑞康医院，广西壮族自治区南宁市  530011；2玉林市中西医结合骨科医院，广西壮族自治区玉林市  537006

  • 收稿日期:2024-10-31 接受日期:2024-12-31 出版日期:2025-12-18 发布日期:2025-05-07
  • 通讯作者: 张驰，博士，主治医师，广西中医药大学附属瑞康医院，广西壮族自治区南宁市 530011
  • 作者简介:韩杰，男，1981年生，广西壮族自治区合浦县人，汉族，硕士，教授，主任医师，主要从事脊柱与四肢退行性病变的中医药防治研究。
  • 基金资助:
    国家自然科学基金项目(82260858，82460872)，项目负责人：韩杰；广西自然科学基金项目(2024GXNSFAA010243)，项目负责人：韩杰；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；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；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；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

Identification of immunodiagnostic biomarkers and drug screening for steroid-induced osteonecrosis of the femoral head

Han Jie1, Pan Chengzhen2, Shang Yuzhi1, Zhang Chi1   

  1. 1Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning 530011, Guangxi Zhuang Autonomous Region, China; 2Yulin Orthopedic Hospital of Integrated Traditional Chinese and Western Medicine, Yulin 537006, Guangxi Zhuang Autonomous Region, China
  • Received:2024-10-31 Accepted:2024-12-31 Online:2025-12-18 Published:2025-05-07
  • Contact: Zhang Chi, MD, Attending physician, Department of Orthopedics, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning 530011, Guangxi Zhuang Autonomous Region, China
  • About author:Han Jie, Master, Professor, Chief physician, Department of Orthopedics, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning 530011, Guangxi Zhuang Autonomous Region, China
  • Supported by:
    National Natural Science Foundation of China, Nos. 82260858 and 82460872 (to HJ); Guangxi Natural Science Foundation, No. 2024GXNSFAA010243 (to HJ); Pilot Project for the High-Level Construction of Key Disciplines of Chinese Medicine in Guangxi, No. [2023]13 (to HJ); Guangxi Key Research Laboratory Construction Project of Traditional Chinese Medicine, No. [2023]9 (to HJ); Guangxi Young Qihuang Scholars Training Project, No. [2022]13 (to HJ); “Qihuang Engineering” High-Level Talent Team Cultivation Project of Guangxi University of Chinese Medicine, No. [2024]3 (to HJ)

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摘要：


文题释义：
激素性股骨头坏死：是指长期使用类固醇药物导致的非创伤性股骨头坏死，主要病因是类固醇药物的长期使用影响股骨头的血液供应，导致股骨头缺血、坏死，最终造成骨组织塌陷。研究表明，大剂量激素治疗，尤其是长期使用糖皮质激素，是引发股骨头坏死的主要危险因素之一。
孟德尔随机化分析：是一种利用与特定暴露相关的遗传变异作为工具变量，以此估计暴露因素与结局之间因果关系的方法，这种暴露相关遗传变异的等位基因是随机分配的，不受反向因果关系的影响。

背景：激素性股骨头坏死的发病机制尚未完全明确，深入了解激素性股骨头坏死的病理及分子机制，寻找高特异性和高灵敏性诊断标志物对于防治激素性股骨头坏死至关重要。
目的：筛选激素性股骨头坏死的免疫诊断标志物，并通过药物富集分析和分子对接技术预测潜在药物靶点。
方法：采用GEO数据库(由美国国家生物技术信息中心搭建的公共的基因表达数据存储库)的GSE123568和GSE74089表达谱数据，利用R软件进行数据归一化和差异基因筛选，应用加权基因共表达网络分析(WGCNA)确定激素性股骨头坏死特征基因。通过GeneCards数据库获取免疫相关基因，并与差异基因和WGCNA基因集取交集，筛选出激素性股骨头坏死免疫相关基因。采用孟德尔随机化验证免疫相关基因与激素性股骨头坏死的潜在因果关系。利用GSEA分析激素性股骨头坏死免疫相关基因参与的免疫相关通路，并通过蛋白互作网络分析其功能关联性。通过药物富集分析和分子对接初步预测疫相关基因的潜在药物。
结果与结论：研究确定了RNASEL、SECTM1和HSPA6三个关键免疫相关基因，这些基因在激素性股骨头坏死中高表达且具有良好的诊断效能，同时参与多条免疫相关信号通路。孟德尔随机化分析验证了免疫相关基因与激素性股骨头坏死的潜在因果关系。通过药物富集分析和分子对接筛选出包括β-七叶素在内的9种潜在药物，显示了通过调控HSPA6蛋白干预激素性股骨头坏死病理过程的可能性。这些发现不仅为激素性股骨头坏死的早期诊断和个性化治疗提供了新的标志物和药物靶点，还展示了生物信息学在中国生物医学研究中的应用潜力，对国际数据在中国疾病研究中有借鉴和转化应用的意义。
https://orcid.org/0000-0003-1750-4400(韩杰)；https://orcid.org/0000-0002-4143-170X(张驰)

中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

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

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.

Key words: bioinformatics analysis, Mendelian randomization, immune-related genes, steroid-induced osteonecrosis of the femoral head, weighted correlation network analysis, engineered tissue construction

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