Weighted Gene Co-expression Network Analysis for RNA-Sequencing Data of the Varicose Veins Transcriptome
Weighted Gene Co-expression Network Analysis for RNA-Sequencing Data of the Varicose Veins Transcriptome
复制标题
静脉曲张转录组 RNA 测序数据的加权基因共表达网络分析
DOI：
10.3389/fphys.2019.00278
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发表时间：
2019-03-19
影响因子：
4
通讯作者：
Liu, Peng
中科院分区：
文献类型：
--
作者：
Zhang, Jianbin;Nie, Qiangqiang;Liu, Peng
目的静脉曲张是一个世界性的常见问题，可导致严重的健康相关生活质量的损害，但病因和发病机制仍然没有得到很好的界定。本研究旨在通过检测差异表达基因、通路和调控基因，阐明静脉曲张的转录调控机制。方法收集行冠状动脉旁路移植术（CABG）和静脉曲张患者的大隐静脉（GSV）。采用RNA测序技术（RNA-Seq）获得CABG患者和曲张静脉GSV的完整转录组学数据。然后进行加权基因共表达网络分析（WGCNA）和进一步的分析，目的是通过检测差异表达的基因、通路和调节基因来阐明静脉曲张的转录调控。结果2015年1月至2016年12月，共获得冠状动脉旁路移植术患者GSV 7条，曲张静脉13条。国民账户工作组确定了4个模块。在棕色模块中，基因本体（GO）分析显示生物过程集中在对刺激的反应、免疫反应和炎症反应等，京都基因和基因组百科全书（KEGG）通路分析显示生物过程集中在嘌呤-细胞因子受体相互作用和TNF信号通路等，在灰色模块中，GO分析表明，生物学过程与骨骼肌原纤维组装有关。免疫组织化学染色显示，与曲张静脉相比，CABG患者GSV中ASC、Caspase-1和NLRP 3的表达明显增加。组织学分析显示，静脉曲张组血管壁、图尼卡膜、图尼卡膜厚度及胶原/平滑肌比值明显增加，弹性纤维/内弹性膜比值明显降低。结论冠状动脉旁路移植术患者曲张静脉和GSV的转录组信息存在明显差异。与CABG患者的GSV相比，静脉曲张中的一些炎症RNA下调。骨骼肌肌原纤维组装通路可能在静脉曲张的发病机制中起重要作用。这些RNA的特性可能为理解静脉曲张的诊断、进展和治疗提供新的靶点。
Objective Varicose veins are a common problem worldwide and can cause significant impairments in health-related quality of life, but the etiology and pathogenesis remain not well defined. This study aims to elucidate transcriptomic regulations of varicose veins by detecting differentially expressed genes, pathways and regulator genes. Methods We harvested great saphenous veins (GSV) from patients who underwent coronary artery bypass grafting (CABG) and varicose veins from conventional stripping surgery. RNA-Sequencing (RNA-Seq) technique was used to obtain the complete transcriptomic data of both GSVs from CABG patients and varicose veins. Weighted Gene Co-expression network analysis (WGCNA) and further analyses were then carried out with the aim to elucidate transcriptomic regulations of varicose veins by detecting differentially expressed genes, pathways and regulator genes. Results From January 2015 to December 2016, 7 GSVs from CABG patients and 13 varicose veins were obtained. WGCNA identified 4 modules. In the brown module, gene ontology (GO) analysis showed that the biological processes were focused on response to stimulus, immune response and inflammatory response, etc. Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis showed that the biological processes were focused on cytokine-cytokine receptor interaction and TNF signaling pathway, etc. In the gray module, GO analysis showed that the biological processes were skeletal myofibril assembly related. The immunohistochemistry staining showed that the expression of ASC, Caspase-1 and NLRP3 were increased in GSVs from CABG patients compared with varicose veins. Histopathological analysis showed that in the varicose veins group, the thickness of vascular wall, tunica intima, tunica media and collagen/smooth muscle ratio were significantly increased, and that the elastic fiber/internal elastic lamina ratio was decreased. Conclusion This study shows that there are clear differences in transcriptomic information between varicose veins and GSVs from CABG patients. Some inflammatory RNAs are down-regulated in varicose veins compared with GSVs from CABG patients. Skeletal myofibril assembly pathway may play a crucial role in the pathogenesis of varicose veins. Characterization of these RNAs may provide new targets for understanding varicose veins diagnosis, progression, and treatment.