实验证实和生物信息学揭示了免疫系统浸润和黄韧带肥厚的生物标志物。
Experimental confirmation and bioinformatics reveal biomarkers of immune system infiltration and hypertrophy ligamentum flavum.
作者信息
Liu Fei, Zhong Min, Yang Lei, Song Chao, Chen Chaoqi, Xu Zhiwei, Zhang Chi, Li Zhifa, Wu Xiaofei, Jiang Chen, Chen Feng, Yan Qian
机构信息
Department of Orthopedics RuiKang Hospital affiliated to Guangxi University of Chinese Medicine Nanning China.
Department of Orthopedics The Affiliated Hospital of Traditional Chinese Medicine of Southwest Medical University Luzhou China.
出版信息
JOR Spine. 2024 Jul 25;7(3):e1354. doi: 10.1002/jsp2.1354. eCollection 2024 Sep.
BACKGROUND
Hypertrophy ligamentum flavum is a prevalent chronic spinal condition that affects middle-aged and older adults. However, the molecular pathways behind this disease are not well comprehended.
OBJECTIVE
The objective of this work is to implement bioinformatics techniques in order to identify crucial biological markers and immune infiltration that are linked to hypertrophy ligamentum flavum. Further, the study aims to experimentally confirm the molecular mechanisms that underlie the hypertrophy ligamentum flavum.
METHODS
The corresponding gene expression profiles (GSE113212) were selected from a comprehensive gene expression database. The gene dataset for hypertrophy ligamentum flavum was acquired from GeneCards. A network of interactions between proteins was created, and an analysis of functional enrichment was conducted using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) databases. An study of hub genes was performed to evaluate the infiltration of immune cells in patient samples compared to tissues from the control group. Finally, samples of the ligamentum flavum were taken with the purpose of validating the expression of important genes in a clinical setting.
RESULTS
Overall, 27 hub genes that were differently expressed were found through molecular biology. The hub genes were found to be enriched in immune response, chemokine-mediated signaling pathways, inflammation, ossification, and fibrosis processes, as demonstrated by GO and KEGG studies. The main signaling pathways involved include the TNF signaling pathway, cytokine-cytokine receptor interaction, and TGF-β signaling pathway. An examination of immunocell infiltration showed notable disparities in B cells (naïve and memory) and activated T cells (CD4 memory) between patients with hypertrophic ligamentum flavum and the control group of healthy individuals. The in vitro validation revealed markedly elevated levels of ossification and fibrosis-related components in the hypertrophy ligamentum flavum group, as compared to the normal group.
CONCLUSION
The TGF-β signaling pathway, TNF signaling pathway, and related hub genes play crucial roles in the progression of ligamentum flavum hypertrophic. Our study may guide future research on fibrosis of the ligamentum flavum.
背景
黄韧带肥厚是一种常见的慢性脊柱疾病，影响中老年人。然而，这种疾病背后的分子途径尚未得到充分理解。
目的
本研究旨在运用生物信息学技术，识别与黄韧带肥厚相关的关键生物标志物和免疫浸润。此外，该研究旨在通过实验证实黄韧带肥厚的分子机制。
方法
从综合基因表达数据库中选择相应的基因表达谱（GSE113212）。黄韧带肥厚的基因数据集来自GeneCards。构建了蛋白质之间的相互作用网络，并使用京都基因与基因组百科全书（KEGG）和基因本体论（GO）数据库进行功能富集分析。进行了枢纽基因研究，以评估患者样本中免疫细胞与对照组组织相比的浸润情况。最后，采集黄韧带样本以验证重要基因在临床环境中的表达。
结果
总体而言，通过分子生物学发现了27个差异表达的枢纽基因。GO和KEGG研究表明，这些枢纽基因在免疫反应、趋化因子介导的信号通路、炎症、骨化和纤维化过程中富集。主要涉及的信号通路包括TNF信号通路、细胞因子 - 细胞因子受体相互作用和TGF-β信号通路。免疫细胞浸润检查显示，肥厚性黄韧带患者与健康个体对照组之间的B细胞（幼稚和记忆）和活化T细胞（CD4记忆）存在显著差异。体外验证显示，与正常组相比，肥厚性黄韧带组中骨化和纤维化相关成分的水平明显升高。
结论
TGF-β信号通路/TNF信号通路及相关枢纽基因在黄韧带肥厚的进展中起关键作用。我们的研究可能为未来黄韧带纤维化的研究提供指导。
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