Luoyang Orthopedic-Traumatological Hospital Of Henan Province, Luoyang, Henan, China.
Funct Integr Genomics. 2023 Sep 1;23(3):289. doi: 10.1007/s10142-023-01216-8.
Lumbar disc herniation (LDH) is the most common condition associated with low back pain, and it adversely impacts individuals' health. Ferroptosis has recently emerged as a novel factor in the pathogenesis of LDH; however, the specific impacts of ferroptosis on LDH have not been fully elucidated. Ferroptosis-related differentially expressed genes (FRDEGs) were identified from the transcriptomic datasets of LDH. Gene set enrichment analysis (GSEA) was conducted to identify biological mechanism and related pathways. LASSO and SVM-RFE algorithms were applied to detect signature genes. Function of the signature gene was confirmed by RT-qPCR. The CIBERSORT algorithm was used to compare immune infiltration between LDH and normal samples. Correlation analysis between MYB and immune cells was analyzed using the Pearson method. Additionally, we used scRNA-seq to dissect cell clusters and cellular interactions. AUCell scoring was used to analyze the ferroptosis scores of different cell types. We found that MYB, a highly expressed ferroptosis-related gene, was associated with LDH By leveraging bioinformatics analysis. In immune infiltration analysis, the abundance of monocytes and macrophages varied significantly between the LDH group and disc spondylolisthesis (DS) group. MYB was correlated with most immune cells. GSEA revealed MYB was significantly enriched in immune-related pathways. Furthermore, scRNA-seq analysis revealed the presence of eight distinct cell types. AUCell analysis showed that macrophages had a high ferroptosis score. Cell trajectory analysis revealed that chondrocyte 1 was at the beginning of the trajectory, while calcification inhibiting chondrocytes and fibrochondrocytes accumulated along the middle and tail end of the trajectory, respectively. Cell-cell communication analysis identified chondrocyte 1 had an extensive communication network with other clusters and interacted with nucleus pulposus through collagen signaling pathway. Our analysis demonstrated that MYB may be a potential therapeutic target for LDH. This study provides a resource for the orthopedics community that will facilitate additional discoveries directedly toward understanding the pathogenesis process of LDH.
腰椎间盘突出症（LDH）是与腰痛相关的最常见疾病，对个人健康有不利影响。铁死亡最近被认为是 LDH 发病机制中的一个新因素；然而，铁死亡对 LDH 的具体影响尚未完全阐明。从 LDH 的转录组数据集确定铁死亡相关差异表达基因（FRDEGs）。进行基因集富集分析（GSEA）以鉴定生物机制和相关途径。应用 LASSO 和 SVM-RFE 算法检测特征基因。通过 RT-qPCR 验证特征基因的功能。使用 CIBERSORT 算法比较 LDH 和正常样本之间的免疫浸润。使用 Pearson 方法分析 MYB 与免疫细胞之间的相关性。此外，我们使用 scRNA-seq 对细胞簇和细胞相互作用进行剖析。使用 AUCell 评分分析不同细胞类型的铁死亡分数。我们发现，高表达的铁死亡相关基因 MYB 与 LDH 相关。通过生物信息学分析。在免疫浸润分析中，LDH 组和椎间盘滑脱（DS）组之间单核细胞和巨噬细胞的丰度差异显著。MYB 与大多数免疫细胞相关。GSEA 表明 MYB 在免疫相关途径中显著富集。此外，scRNA-seq 分析揭示了存在八种不同的细胞类型。AUCell 分析表明巨噬细胞的铁死亡分数较高。细胞轨迹分析表明，软骨细胞 1 处于轨迹的开始，而钙化抑制软骨细胞和纤维软骨细胞分别沿着轨迹的中间和尾部积累。细胞间通讯分析表明，软骨细胞 1 与其他簇有广泛的通讯网络，并通过胶原蛋白信号通路与髓核相互作用。我们的分析表明，MYB 可能是 LDH 的潜在治疗靶点。本研究为骨科领域提供了一个资源，将有助于进一步发现直接理解 LDH 发病机制的过程。
