Li Zijian, Cui Yueran, Feng Juan, Guo Yanxia
Department of Neurology, Shengjing Hospital of China Medical University, No. 36 Sanhao Street, Heping District, Shenyang, 110004, Liaoning, People's Republic of China.
J Transl Med. 2020 Aug 3;18(1):296. doi: 10.1186/s12967-020-02463-0.
Ischemic stroke (IS) is the second leading cause of death worldwide which is a serious hazard to human health. Evidence suggests that the immune system plays a key role in the pathophysiology of IS. However, the precisely immune related mechanisms were still not been systematically understood.
In this study, we aim to identify the immune related modules and genes that might play vital role in the occurrence and development of IS by using the weighted gene co-expression network analysis (WGCNA). Meanwhile, we applied a kind of deconvolution algorithm to reveal the proportions of 22 subsets of immune cells in the blood samples.
There were total 128 IS patients and 67 healthy control samples in the three Gene Expression Omnibus (GEO) datasets. Under the screening criteria, 1082 DEGs (894 up-regulated and 188 down-regulated) were chosen for further analysis. A total of 11 clinically significant modules were identified, from which immune-related hub modules and hub genes were further explored. Finally, 16 genes were selected as real hub genes for further validation analysis. Furthermore, these CIBERSORT results suggest that detailed analysis of the immune subtype distribution pattern has the potential to enhance clinical prediction and to identify candidates for immunotherapy. More specifically, we identified that neutrophil emerge as a promising target for IS therapies.
In the present study, we investigated the immune related gene expression modules, in which the SLAMF1, IL7R and NCF4 may be novel therapeutic targets to promote functional and histological recovery after ischemic stroke. Furthermore, these hub genes and neutrophils may become important biological targets in the drug screening and drug designing.
缺血性中风(IS)是全球第二大致死原因,对人类健康构成严重威胁。有证据表明,免疫系统在IS的病理生理学中起关键作用。然而,确切的免疫相关机制仍未得到系统的理解。
在本研究中,我们旨在通过使用加权基因共表达网络分析(WGCNA)来识别可能在IS的发生和发展中起重要作用的免疫相关模块和基因。同时,我们应用一种反卷积算法来揭示血液样本中22种免疫细胞亚群的比例。
三个基因表达综合数据库(GEO)数据集中共有128例IS患者和67例健康对照样本。根据筛选标准,选择了1082个差异表达基因(DEG)(894个上调和188个下调)进行进一步分析。共鉴定出11个具有临床意义的模块,从中进一步探索了免疫相关的枢纽模块和枢纽基因。最后,选择了16个基因作为真正的枢纽基因进行进一步的验证分析。此外,这些CIBERSORT结果表明,对免疫亚型分布模式的详细分析有可能提高临床预测能力并识别免疫治疗的候选者。更具体地说,我们确定中性粒细胞是IS治疗的一个有希望的靶点。
在本研究中,我们研究了免疫相关基因表达模块,其中信号淋巴细胞激活分子家族成员1(SLAMF1)、白细胞介素7受体(IL7R)和中性粒细胞胞质因子4(NCF4)可能是促进缺血性中风后功能和组织学恢复的新治疗靶点。此外,这些枢纽基因和中性粒细胞可能成为药物筛选和药物设计中的重要生物学靶点。