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目的 椎间盘退变(intervertebral disc degeneration, IDD)发病机制尚不明确，但遗传因素被认为是IDD的可能病因之一。本研究旨在识别遗传风险因素并建立诊断模型。方法 基于基因表达综合数据库(gene expression omnibus, GEO)的表达谱数据集筛选出差异表达基因(differentially expressed genes, DEGs)和坏死性凋亡相关基因(necroptosis-related genes, NRDEGs),并构建NRDEGs诊断模型用于预测IDD患者的预后。结果 本研究筛选出16个NRDEGs,其中12个NRDEGs可能潜在地参与IDD的发病机制，并发现了潜在的治疗靶基因，特别是SQSTM1基因。基于NRDEGs构建的诊断模型计算出12个Co-NRDEGs的风险评分，并通过CTD数据库检索出8个关键基因关联的43种潜在药物或分子化合物，其中28种靶向SQSTM1基因。作为血管平滑肌细胞自噬与衰老的主要调控因子SQSTM1/p62基因在骨骼代谢过程中发挥关键作用。结论 通过对IDD进行严格的数据预处理，揭示了IDD的分子机制。构建的强大诊断模型在区分IDD风险组方面表现出高准确性，为脊柱疾病领域的进一步研究和潜在的治疗干预奠定了基础。
Abstract：Objective The pathogenesis of intervertebral disc degeneration(IDD) remains unclear, but genetic factors are considered one of the potential etiological factors.This study aims to identify genetic risk factors and establish a diagnostic model for IDD.Methods Expression profile datasets from the Gene Expression Omnibus(GEO) database were utilized to screen for differentially expressed genes(DEGs) and necroptosis-related differentially expressed genes(NRDEGs).Subsequently, a diagnostic model based on these NRDEGs was constructed to predict the prognosis of patients with IDD.Results Sixteen NRDEGs were identified, among which 12 may be involved in the pathogenesis of IDD.Potential therapeutic target genes were also discovered, with a particular focus on sequestosome 1(SQSTM1).A diagnostic model constructed based on the NRDEGs was used to calculate risk scores from 12 co-expressed necroptosis-related differentially expressed genes(Co-NRDEGs).Through the Comparative Toxicogenomics Database(CTD),43 potential drugs or molecular compounds associated with 8 key genes were retrieved, 28 of which target the SQSTM1 gene.As a major regulator of autophagy and senescence in vascular smooth muscle cells, the SQSTM1/p62 gene plays a crucial role in skeletal metabolism.Conclusion Through rigorous data preprocessing, this study elucidated the molecular mechanisms underlying IDD.The robust diagnostic model we constructed demonstrated high accuracy in distinguishing among IDD risk groups, laying a foundation for further research and potential therapeutic interventions in the field of spinal diseases.
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基本信息:
DOI：10.16846/j.issn.1004-3101.2026.01.002
中图分类号:R681.55
引用信息:
[1]潘洪发,李凯男,高梅,等.椎间盘退变中坏死性凋亡相关遗传风险因素分析及诊断模型研究[J].山东第二医科大学学报,2026,48(01):8-16.DOI:10.16846/j.issn.1004-3101.2026.01.002.
基金信息:
潍坊市科技发展计划项目(项目编号：2021YX098);潍坊市科技发展计划项目(项目编号：2023YX015)
2026-02-15
2026-02-15