中国组织工程研究 ›› 2024, Vol. 28 ›› Issue (28): 4505-4510.doi: 10.12307/2024.431

• 组织工程相关大数据分析 Big data analysis in tissue engineering • 上一篇    下一篇

泛凋亡因子在骨质疏松症中的诊断标记物及亚型分析

丁  强1,熊  波1,刘金富2,田  照1,容向宾3,陈立民1,陶红成1,李  豪1,曾  平2   

  1. 1广西中医药大学第一临床医学院,广西壮族自治区南宁市  530000;2广西中医药大学第一附属医院,广西壮族自治区南宁市  530000;3广西中医药大学附属瑞康医院,广西壮族自治区南宁市  530000
  • 收稿日期:2023-06-05 接受日期:2023-07-27 出版日期:2024-10-08 发布日期:2023-11-27
  • 通讯作者: 曾平,博士,主任医师,广西中医药大学第一附属医院,广西壮族自治区南宁市 530000
  • 作者简介:丁强,男,1995年生,广西中医药大学在读博士,主要从事骨坏死与退行性疾病的防治研究。
  • 基金资助:
    国家自然科学基金项目(81960876),项目负责人:曾平;广西壮族自治区级博士创新课题(YCBZ2023152),项目负责人:丁强

Molecular mechanism of PANoptosis in diagnostic markers and subtyping of osteoporosis

Ding Qiang1, Xiong Bo1, Liu Jinfu2, Tian Zhao1, Rong Xiangbin3, Chen Limin1, Tao Hongcheng1, Li Hao1, Zeng Ping2   

  1. 1The First Clinical Medical College of Guangxi University of Chinese Medicine, Nanning 530000, Guangxi Zhuang Autonomous Region, China; 2The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning 530000, Guangxi Zhuang Autonomous Region, China; 3Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning 530000, Guangxi Zhuang Autonomous Region, China
  • Received:2023-06-05 Accepted:2023-07-27 Online:2024-10-08 Published:2023-11-27
  • Contact: Zeng Ping, MD, Chief physician, The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning 530000, Guangxi Zhuang Autonomous Region, China
  • About author:Ding Qiang, MD candidate, The First Clinical Medical College of Guangxi University of Chinese Medicine, Nanning 530000, Guangxi Zhuang Autonomous Region, China
  • Supported by:
    National Natural Science Foundation of China, No. 81960876 (to ZP); Doctoral Innovation Project of Guangxi Zhuang Autonomous Region, No. YCBZ2023152 (to DQ)

摘要:


文题释义:

骨质疏松症:是一种以骨密度降低,易于发生骨折为特征的骨骼疾病,随着人口结构的变化,骨质疏松症正在成为全球卫生保健的一个日益增加的负担,若早期诊断与防治有望取得良好的临床疗效,因此寻找可靠的诊断生物标志物是目前值得关注的问题。 
泛凋亡(PANoptosis):是基于对炎症小体/焦亡与凋亡和坏死性凋亡之间交互作用的研究而建立的概念。它是一种炎症性程序细胞死亡,受到泛凋亡复合体的调控,具有细胞焦亡、凋亡和/或坏死性凋亡的关键特征,且不能被焦亡、凋亡和坏死性凋亡中任意一种死亡方式单独表征。


背景:研究推测泛凋亡可能参与了骨质疏松的病理过程,但目前尚未有泛凋亡基因在骨质疏松中的相关机制研究。

目的:分析泛凋亡调节因子在骨质疏松症发生发展过程中的生物学机制。   
方法:从Gene Expresion omnibus(GEO)数据库中获得GSE56815数据集,提取泛凋亡基因进行差异分析。通过随机森林树模型筛选泛凋亡关键基因,构建疾病风险预测模型。运用共识聚类算法、单样本基因组富集分析以及免疫浸润分析探讨不同泛凋亡分子亚型间的差异性。通过医学本体信息检索平台 Coremine medical 数据库预测调节泛凋亡关键基因的中药药物。

结果与结论:①基于4个泛凋亡关键基因(CASP1、CASP10、MEFV、TNF),确定了骨质疏松症中的诊断标志物,构建了患病风险预测模型并进行验证;②将骨质疏松患者分为2种不同的泛凋亡亚型(簇A、B和基因簇A、B),且簇B和基因簇B的泛凋亡评分分别高于簇A和基因簇A;③通过 Coremine medical 数据库预测出人参等能调节泛凋亡关键基因的中药药物。

https://orcid.org/0009-0008-7591-4313(丁强)

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: 骨质疏松症, 泛凋亡, 预测模型, 分子亚型, 中药预测

Abstract: BACKGROUND: It has been hypothesized that PANoptosis may be involved in the pathologic process of osteoporosis, but there have been no studies addressing the mechanisms of PANoptosis genes in osteoporosis.
OBJECTIVE: To analyze the biological mechanism of PANoptosis regulators in the occurrence and development of osteoporosis. 
METHODS: The GSE56815 dataset was obtained from the Gene Expression Omnibus database and PANoptosis genes were extracted for differential analysis. The key genes of PANoptosis were screened by random forest tree model to construct a disease risk prediction model. Consensus clustering algorithm, single sample genome enrichment analysis and immune infiltration analysis were used to explore the differences between different PANoptosis molecular subtypes. Herbal drugs that regulate the key genes of PANoptosis were predicted through Coremine medical database, a medical ontology information retrieval platform. 
RESULTS AND CONCLUSION: Based on the four PANoptosis key genes (CASP1, CASP10, MEFV, and TNF), the diagnostic markers of osteoporosis were determined, and the risk prediction model was constructed and verified. Osteoporosis was divided into two different PANoptosis subtypes (clusters A, B and gene clusters A, B), and the PANoptosis scores of cluster B and gene cluster B were higher than those of cluster A and gene cluster A, respectively. Traditional Chinese drugs such as ginseng which can regulate the key genes of PANoptosis were predicted by the Coremine medical database.

Key words: osteoporosis, PANoptosis, prediction model, molecular subtype, traditional Chinese medicine prediction

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