Consensus clustering of gene expression profiles in peripheral blood of acute ischemic stroke patients.
Consensus clustering of gene expression profiles in peripheral blood of acute ischemic stroke patients.
复制标题
DOI：
10.3389/fneur.2022.937501
复制
发表时间：
2022
影响因子：
3.4
通讯作者：
Huang, Li'an
中科院分区：
文献类型：
--
作者：
Yang, Zhiyong;Wang, Guanghui;Luo, Nan;Tsang, Chi Kwan;Huang, Li'an
关键词：
急性缺血性脑卒中（AIS）是世界范围内死亡率和发病率的主要原因。目前，尚无临床批准的免疫干预措施可用于AIS治疗，部分原因是缺乏基于AIS患者外周免疫状态的相关患者分类。在本研究中，我们采用共识聚类方法，根据外周血转录组谱将AIS患者划分为分子亚组，并通过加权基因共表达网络分析确定了3个不同的AIS分子亚组，每个亚组中有8个模块。值得注意的是，预先排序的基因集富集分析显示，在AIS患者出血转化（HT）中，具有亚群i特异性特征基因的共表达模块与差异表达基因显著重叠。至于亚组II，只有男性患者的蛋白酶体活性下降被确定。有趣的是，大多数III亚组由女性患者组成，她们表现出相对较低水平的ais诱导的免疫抑制（AIIS）。此外，我们发现女性年龄与亚群特异性基因表达之间存在非线性关系，表明外周免疫存在性别和年龄依赖性改变。综上所述，我们的新AIS分类方法可以促进免疫调节治疗，包括给予性别特异性治疗，并降低缺血性卒中后HT和AIIS的风险。
Acute ischemic stroke (AIS) is a primary cause of mortality and morbidity worldwide. Currently, no clinically approved immune intervention is available for AIS treatment, partly due to the lack of relevant patient classification based on the peripheral immunity status of patients with AIS. In this study, we adopted the consensus clustering approach to classify patients with AIS into molecular subgroups based on the transcriptomic profiles of peripheral blood, and we identified three distinct AIS molecular subgroups and 8 modules in each subgroup by the weighted gene co-expression network analysis. Remarkably, the pre-ranked gene set enrichment analysis revealed that the co-expression modules with subgroup I-specific signature genes significantly overlapped with the differentially expressed genes in AIS patients with hemorrhagic transformation (HT). With respect to subgroup II, exclusively male patients with decreased proteasome activity were identified. Intriguingly, the majority of subgroup III was composed of female patients who showed a comparatively lower level of AIS-induced immunosuppression (AIIS). In addition, we discovered a non-linear relationship between female age and subgroup-specific gene expression, suggesting a gender- and age-dependent alteration of peripheral immunity. Taken together, our novel AIS classification approach could facilitate immunomodulatory therapies, including the administration of gender-specific therapeutics, and attenuation of the risk of HT and AIIS after ischemic stroke.
登录
查看更多内容
影响因子：
4.8
作者：
Falcione S;Kamtchum-Tatuene J;Sykes G;Jickling GC
通讯作者：
Jickling GC
影响因子：
2.7
作者：
Andersson A;Edén P;Olofsson T;Fioretos T
通讯作者：
Fioretos T
影响因子：
4.2
作者：
Esteras, Noemi;Alquezar, Carolina;Martin-Requero, Angeles
通讯作者：
Martin-Requero, Angeles
影响因子：
3.8
作者：
Galimberti, D.;Fenoglio, C.;Scarpini, E.
通讯作者：
Scarpini, E.
DOI：
10.1093/humrep/deab123
发表时间：
2021-07-19
期刊：
Human reproduction (Oxford, England)
影响因子：
--
作者：
Giacomini E;Scotti GM;Vanni VS;Lazarevic D;Makieva S;Privitera L;Signorelli S;Cantone L;Bollati V;Murdica V;Tonon G;Papaleo E;Candiani M;Viganò P
通讯作者：
Viganò P