Li Wen-Xing, Qi Fei, Liu Jia-Qian, Li Gong-Hua, Dai Shao-Xing, Zhang Tao, Cheng Fei, Liu Dahai, Zheng Song Guo
Institute of Health Sciences, Anhui UniversityHefei 230601, Anhui, China; State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of SciencesKunming 650223, Yunnan, China.
Department of Respiratory Medicine, Guizhou Medical University Guiyang 550004, Guizhou, China.
Am J Transl Res. 2017 Feb 15;9(2):736-745. eCollection 2017.
Ischemic stroke therapy and prognosis outcomes largely depend on the time periods after symptom onset. This study aims to explore the difference of global gene expression profiles and impairment of biological functions between short-term and long-term after stroke onset. We compared three short-term (3 h, 5 h and 24 h) and a long-term (6-month) gene expression levels by a multi-platform microarray data integration method. RankProd was used to calculate the differentially expressed genes between stroke patients and controls. DAVID Bioinformatics Resources was utilized to determine affected biological functions. Consensus cluster and hierarchical cluster methods were employed to compare the gene expression patterns of the commonly biological functions among these four time course groups. The results showed that severe impairment of inflammation and immune related functions in 5 h and 24 h after symptom onset. However, these functions were less affected in the 3 h and the 6-month groups. In addition, several key genes (CCL20, THBS1, EREG, and IL6 et al.) were dramatically down-regulated in 5 h and 24 h groups, whereas these genes showed no change or even a slight contrary expression in 3 h or 6-month groups. This study has identified the large differences of altered immune and inflammation functions based on gene levels between short and long-term after stroke onset. The findings provide valuable insight into the clinical practice and prognosis evaluation of ischemic stroke.
缺血性中风的治疗和预后结果很大程度上取决于症状发作后的时间段。本研究旨在探讨中风发作后短期和长期之间全球基因表达谱的差异以及生物学功能的损伤情况。我们采用多平台微阵列数据整合方法比较了三个短期(3小时、5小时和24小时)和一个长期(6个月)的基因表达水平。使用RankProd计算中风患者与对照组之间的差异表达基因。利用DAVID生物信息学资源确定受影响的生物学功能。采用共识聚类和层次聚类方法比较这四个时间进程组中常见生物学功能的基因表达模式。结果显示,症状发作后5小时和24小时炎症和免疫相关功能严重受损。然而,这些功能在3小时组和6个月组中受影响较小。此外,几个关键基因(CCL20、THBS1、EREG和IL6等)在5小时和24小时组中显著下调,而这些基因在3小时组或6个月组中无变化甚至有轻微相反表达。本研究确定了中风发作后短期和长期基于基因水平的免疫和炎症功能改变的巨大差异。这些发现为缺血性中风的临床实践和预后评估提供了有价值的见解。