Li Weihang, Ding Ziyi, Zhang Huan, Shi Quan, Wang Dong, Zhang Shilei, Xu Songjie, Gao Bo, Yan Ming
Department of Orthopedic Surgery, Xijing Hospital, Air Force Medical University, Xi'an, China.
Department of Orthopaedics, Affiliated Hospital of Yanan University, Yanan, China.
Front Cell Dev Biol. 2022 Feb 9;10:844395. doi: 10.3389/fcell.2022.844395. eCollection 2022.
Intervertebral disc degeneration is a progressive and chronic disease, usually manifesting as low back pain. This study aimed to screen effective biomarkers for medical practice as well as figuring out immune infiltration situations between circulation and intervertebral discs. Gene expression profiles of GSE124272 was included for differentially analysis, WGCNA and immune infiltration analysis from GEO database, and other GSE series were used as validation datasets. A series of validation methods were conducted to verify the robustness of hub genes, such as principal component analysis, machine learning models, and expression verification. Lastly, nomogram was established for medical practice. 10 genes were commonly screened combination of DEGs, WGCNA analysis and lipid metabolism related genes. Furthermore, 3 hub gens CYP27A1, FAR2, CYP1B1 were chosen for subsequent analysis based on validation of different methods. GSEA analysis discovered that neutrophil extracellular traps formation and NOD-like receptor signaling pathway was activated during IDD. Immune infiltration analysis demonstrated that the imbalance of neutrophils and γδT cells were significantly correlated with IDD progression. Nomogram was established based on CYP27A1, FAR2, CYP1B1 and age, the calibration plot confirmed the stability of our model. CYP27A1, FAR2, CYP1B1 were considered as hub lipid metabolism related genes (LMRGs) in the development of IDD, which were regarded as candidate diagnostic biomarkers especially in circulation. The effects are worth expected in the early diagnosis of IDD through detecting these genes in blood.
椎间盘退变是一种进行性慢性疾病,通常表现为腰痛。本研究旨在筛选出对医疗实践有效的生物标志物,并弄清楚循环系统与椎间盘之间的免疫浸润情况。纳入GSE124272的基因表达谱进行差异分析、加权基因共表达网络分析(WGCNA)以及来自基因表达综合数据库(GEO)的免疫浸润分析,并将其他GSE系列用作验证数据集。采用一系列验证方法来验证枢纽基因的稳健性,如主成分分析、机器学习模型和表达验证。最后,建立列线图用于医疗实践。通过对差异表达基因(DEGs)、WGCNA分析和脂质代谢相关基因的组合分析,共筛选出10个基因。此外,基于不同方法的验证,选择了3个枢纽基因CYP27A1、FAR2、CYP1B1进行后续分析。基因集富集分析(GSEA)发现,在椎间盘退变过程中中性粒细胞胞外诱捕网形成和NOD样受体信号通路被激活。免疫浸润分析表明,中性粒细胞和γδT细胞的失衡与椎间盘退变进展显著相关。基于CYP27A1、FAR2、CYP1B1和年龄建立了列线图,校准图证实了我们模型的稳定性。CYP27A1、FAR2、CYP1B1被认为是椎间盘退变发展过程中与脂质代谢相关的枢纽基因(LMRGs),尤其是在循环系统中,它们被视为候选诊断生物标志物。通过检测血液中的这些基因,有望在椎间盘退变的早期诊断中发挥作用。