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通过代谢组学和转录组学的综合分析深入了解骨关节炎。

Insight into osteoarthritis through integrative analysis of metabolomics and transcriptomics.

机构信息

Department of Acupuncture and Rehabilitation, Guangzhou Hospital of Integrated Traditional Chinese and Western Medicine, Guangzhou, Guangdong 510000, PR China.

International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, PR China.

出版信息

Clin Chim Acta. 2020 Nov;510:323-329. doi: 10.1016/j.cca.2020.07.010. Epub 2020 Jul 10.

DOI:10.1016/j.cca.2020.07.010
PMID:32653484
Abstract

Lack of clinically specific biomarkers has impeded the diagnosis of osteoarthritis (OA) and limited understanding of pathogenesis for OA has also restrained the enhancement of therapeutic measures. In the study, plasma untargeted metabolomics of twelve OA patients and twenty healthy controls (HC) were analyzed by gas chromatography coupled with quadrupole time-of-flight mass spectrometry (GC/Q-TOF-MS). The differential metabolites (DMs) between OA and HC were evaluated by multivariate analysis and Bayes discriminant analysis was employed to discover potential diagnosis biomarkers. Meanwhile a transcriptomic dataset GSE55235 was downloaded from GEO database to explore the differentially expressed genes (DEGs) between OA and HC by R/Bioconductor project. Finally, an integrative analysis of DMs and DEGs was performed to investigate the possible molecular mechanisms of OA. As a result, a panel of three metabolites including succinic acid, xanthurenic acid and L-tryptophan was revealed to potentially act as biomarker for the diagnosis of OA. Furthermore, the integrated analysis of metabolomics and transcriptomics showed the top three enrichment in the T cell receptor signaling pathway, Fc epsilon RI (FcεRI) signaling pathway, and thermogenesis, explaining the inflammation, joint destruction and energy metabolism disorders in OA.

摘要

缺乏临床特异性生物标志物阻碍了骨关节炎 (OA) 的诊断,对 OA 发病机制的了解有限也限制了治疗措施的加强。在这项研究中,采用气相色谱 - 四极杆飞行时间质谱联用技术 (GC/Q-TOF-MS) 对 12 例 OA 患者和 20 例健康对照者 (HC) 的血浆非靶向代谢组学进行了分析。通过多元分析评估 OA 和 HC 之间的差异代谢物 (DM),并采用贝叶斯判别分析来发现潜在的诊断生物标志物。同时,从 GEO 数据库下载转录组数据集 GSE55235,通过 R/Bioconductor 项目探索 OA 和 HC 之间的差异表达基因 (DEGs)。最后,对 DM 和 DEGs 进行综合分析,以研究 OA 的可能分子机制。结果表明,一组包括琥珀酸、黄尿酸和 L-色氨酸在内的三种代谢物可能作为 OA 诊断的生物标志物。此外,代谢组学和转录组学的综合分析显示,T 细胞受体信号通路、FcεRI 信号通路和生热作用的前三个富集,解释了 OA 中的炎症、关节破坏和能量代谢紊乱。

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