Department of Pathology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. China.
Department of Blood Transfusion, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. China.
J Cell Biochem. 2019 Sep;120(9):15182-15189. doi: 10.1002/jcb.28780. Epub 2019 Apr 24.
Stroke is one of the most destructive complications of sickle cell disease (SCD), and SCD is also the most common cause of childhood stroke. Sickle cell stroke is complex and has a genetic endothelial basis. Here, we further investigated this genetic basis using weighted gene coexpression network analysis. This systems biology approach revealed the correlation between coexpressed gene modules and sickle stroke risk. The pink module was significantly correlated with stroke risk and genes in this module were mainly related to GO:0044877 (protein-containing complex binding). In addition hub genes were identified through protein-protein interaction enrichment analysis, including CXCR7, VCAM1, CD44, BMP2, SMAD3, BCL2L1, ITPR2, ITPR3, etc. These hub genes were significantly enriched for three Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways including "gastric acid secretion," "pathways in cancer," and "TGF- β signaling pathway." Altogether, our results based on this innovative method provided some novel understanding of the pathology of sickle cell stroke. Hub genes identified in this study could be potential targets for screening and prevention of stroke risk in SCD children.
中风是镰状细胞病（SCD）最具破坏性的并发症之一，SCD 也是儿童中风的最常见原因。镰状细胞性中风很复杂，具有遗传内皮基础。在这里，我们使用加权基因共表达网络分析进一步研究了这种遗传基础。这种系统生物学方法揭示了共表达基因模块与镰状细胞中风风险之间的相关性。粉红色模块与中风风险显著相关，该模块中的基因主要与 GO：0044877（含有蛋白质的复合物结合）有关。此外，通过蛋白质-蛋白质相互作用富集分析鉴定了枢纽基因，包括 CXCR7、VCAM1、CD44、BMP2、SMAD3、BCL2L1、ITPR2、ITPR3 等。这些枢纽基因在三个京都基因与基因组百科全书（KEGG）途径中显著富集，包括“胃酸分泌”、“癌症途径”和“TGF-β 信号通路”。总的来说，我们基于这种创新方法的结果为镰状细胞中风的病理提供了一些新的认识。本研究中鉴定的枢纽基因可能是 SCD 儿童中风风险筛查和预防的潜在靶点。
