Chen Shaofeng, Zhang Wei, Liu Yifan, Huang Runzhi, Zhou Xiaoyi, Wei Xianzhao
Department of Orthopaedic Surgery, Changhai Hospital, Shanghai, China.
Department of Orthopaedic Surgery, China Coast Guard Hospital, Zhejiang, China.
J Transl Med. 2025 Feb 25;23(1):227. doi: 10.1186/s12967-025-06225-8.
Intervertebral disc degeneration (IVDD) is a significant cause of global disability, reducing labor productivity, increasing the burden on public health, and affecting socio-economic well-being. Currently, there is a lack of recognized clinical approaches for molecular classification and precision therapy.
Chondrocyte differentiation and prognosis-related genes were extracted from single-cell RNA sequencing and multi-omics data in the Gene Expression Omnibus (GEO) database through chondrocyte trajectory analysis and non-parametric tests. Subsequently, a precise IVDD risk stratification system was developed using ConsensusClusterPlus analysis. The clinical significance of molecular typing was demonstrated through case-control trials involving IVDD patients. Specific inhibitors of molecular typing were predicted using the pRRophetic package in R language and then validated in vitro.
A stratified model for IVDD, considering chondrocyte differentiation and demonstrating high clinical relevance, was developed using a set of 44 chondrocyte fate genes. Extensive analyses of multi-omics data confirmed the clinical relevance of this model, indicating that cases in the High Chondrocyte Scoring Classification (HCSC) group had the most favorable prognosis, whereas those in the Low Chondrocyte Scoring Classification (LCSC) group had the worst prognosis. Additionally, clinical case-control studies provided evidence of the utility of IVDD molecular typing in translational medicine. A gene expression-based molecular typing approach was used to create a matrix identifying potential inhibitors specific to each IVDD subtype. In vitro experiments revealed that gefitinib, a drug designed for LCSC, not only had protective effects on chondrocytes but also could induce the conversion of LCSC into the HCSC subgroup. Therefore, IVDD molecular typing played a critical role in assisting clinicians with risk stratification and enabling personalized treatment decisions.
The results of the study have provided a comprehensive and clinically relevant molecular typing for IVDD, involving a precise stratification system that offers a new opportunity for customizing personalized treatments for IVDD.
椎间盘退变（IVDD）是导致全球残疾的重要原因，降低了劳动生产率，增加了公共卫生负担，并影响社会经济福祉。目前，缺乏用于分子分类和精准治疗的公认临床方法。
通过软骨细胞轨迹分析和非参数检验，从基因表达综合数据库（GEO）中的单细胞RNA测序和多组学数据中提取软骨细胞分化和预后相关基因。随后，使用ConsensusClusterPlus分析开发了精确的IVDD风险分层系统。通过涉及IVDD患者的病例对照试验证明了分子分型的临床意义。使用R语言中的pRRophetic软件包预测分子分型的特异性抑制剂，然后在体外进行验证。
使用一组44个软骨细胞命运基因建立了一个考虑软骨细胞分化且具有高度临床相关性的IVDD分层模型。对多组学数据的广泛分析证实了该模型的临床相关性，表明高软骨细胞评分分类（HCSC）组的病例预后最佳，而低软骨细胞评分分类（LCSC）组的病例预后最差。此外，临床病例对照研究提供了IVDD分子分型在转化医学中效用的证据。基于基因表达的分子分型方法用于创建一个矩阵，识别每种IVDD亚型特有的潜在抑制剂。体外实验表明，一种针对LCSC设计的药物吉非替尼不仅对软骨细胞有保护作用，还能诱导LCSC转化为HCSC亚组。因此，IVDD分子分型在协助临床医生进行风险分层和做出个性化治疗决策方面发挥了关键作用。
该研究结果为IVDD提供了一个全面且具有临床相关性的分子分型，涉及一个精确的分层系统，为定制IVDD的个性化治疗提供了新机会。
