The Department of Internal Medicine of Traditional Chinese Medicine, College of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, Guangdong, China.
The Department of Rheumatology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China.
Clin Rheumatol. 2019 Sep;38(9):2629-2635. doi: 10.1007/s10067-019-04533-1. Epub 2019 Apr 22.
Rheumatoid arthritis (RA) is a common disease of rheumatic diseases. The aim of this study was to identify gene signatures in RA and uncover their potential mechanisms.
Gene expression profiles of GSE1919, GSE55235, GSE55457, and GSE77928 were downloaded from GEO database. The above four series contained 76 samples, including 44 RA patients and 32 normal controls. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed, and protein-protein interaction (PPI) network of the differentially expressed genes (DEGs) was constructed by Cytoscape software.
Up-regulated DEGs were significantly enriched in biological processes, including immune response, positive regulation of immune system process and regulation of immune system process, while down-regulated DEGs were significantly enriched in biological processes, including response to oxygen-containing compound, cellular lipid metabolic process, and lipid metabolic process. KEGG pathway analysis showed the up-regulated DEGs were enriched in cytokine-cytokine receptor interaction, chemokine signaling pathway, and primary immunodeficiency. The 104 hub genes, which were significantly differently expressed between patients and normal controls in at least two datasets, were identified from the PPI network, and subnetworks revealed that these genes were involved in significant pathways, including cytokine-cytokine receptor interaction, chemokine signaling pathway, and primary immunodeficiency.
The present study indicated that the identified DEGs and hub genes promote our understanding of molecular mechanisms underlying the development of RA, such as C-C motif chemokine 5 (CCL5), might have a negative impact in the development of RA. CCL5 and its related genes might be the potential diagnostic biomarkers for the therapeutic strategies of RA.
类风湿关节炎(RA)是一种常见的风湿性疾病。本研究旨在鉴定 RA 中的基因特征,并揭示其潜在机制。
从 GEO 数据库下载 GSE1919、GSE55235、GSE55457 和 GSE77928 基因表达谱。上述四个系列包含 76 个样本,包括 44 例 RA 患者和 32 例正常对照。进行基因本体(GO)和京都基因与基因组百科全书(KEGG)通路富集分析,并使用 Cytoscape 软件构建差异表达基因(DEGs)的蛋白质-蛋白质相互作用(PPI)网络。
上调的 DEGs 显著富集于生物学过程,包括免疫反应、免疫系统过程的正调控和免疫系统过程的调节,而下调的 DEGs 则显著富集于生物学过程,包括对含氧化合物的反应、细胞脂质代谢过程和脂质代谢过程。KEGG 通路分析表明,上调的 DEGs 富集于细胞因子-细胞因子受体相互作用、趋化因子信号通路和原发性免疫缺陷。从 PPI 网络中鉴定出 104 个在至少两个数据集之间患者与正常对照之间表达差异显著的枢纽基因,子网络显示这些基因参与了重要通路,包括细胞因子-细胞因子受体相互作用、趋化因子信号通路和原发性免疫缺陷。
本研究表明,所鉴定的 DEGs 和枢纽基因有助于我们理解 RA 发病的分子机制,例如 C-C 基序趋化因子 5(CCL5),可能对 RA 的发生有负面影响。CCL5 及其相关基因可能是 RA 治疗策略的潜在诊断生物标志物。