Abstract：
Thrombosis is a major cause of morbimortality in patients with polycythemia vera (PV). Furthermore, neutrophils play a significant role in thrombosis, but their role in the pathogenetic mechanisms of PV is not well characterized. Therefore, we investigated the role and mechanisms by which neutrophils regulate thrombosis in PV patients. Univariate and multivariate logistic regression analysis of clinicopathological factors was performed to determine the independent risk factors of thrombosis in PV. Pearson\'s correlation analysis was performed to determine the relationship between absolute neutrophil count (ANC) and the hypercoagulable state in PV patients. Bioinformatics analysis of the GSE54644 dataset was used to identify hemostasis-related pathways in neutrophils of PV patients. Weighted gene co-expression network analysis (WGCNA) of the integrated dataset (GSE57793, GSE26049 and GSE61629) was used to identify neutrophils-related genes and pathways associated with thrombosis in PV. Ingenuity pathway analysis (IPA) was performed to identify the differentially activated pathways in PV patients with or without thrombosis using GSE47018 dataset. Our data showed increased ANC in PV patients. Multivariate logistic regression analysis showed that ANC was an independent risk factor for the thrombotic events in PV patients before or at diagnosis. ANC correlated with the hypercoagulable state in PV patients. Neutrophil extracellular traps (NETs) pathway was significantly enriched in the neutrophils of PV patients. IPA results demonstrated that PRKCD-mediated NETs pathway was hyperactivated in PV patients with thrombosis. In summary, ANC was an independent risk factor for the thrombotic events in PV patients before or at diagnosis, and PRKCD-mediated NETs pathway was aberrantly activated in the neutrophils of PV patients and was associated with the thrombotic events.
摘要：
血栓形成是真性红细胞增多症（PV）患者病态的主要原因。此外，中性粒细胞在血栓形成中起重要作用，但它们在PV发病机制中的作用还没有得到很好的表征。因此,我们研究了中性粒细胞调节PV患者血栓形成的作用和机制.对临床病理因素进行单因素和多因素logistic回归分析以确定肺静脉血栓形成的独立危险因素。采用Pearson相关分析确定PV患者中性粒细胞绝对计数(ANC)与高凝状态的关系。GSE54644数据集的生物信息学分析用于鉴定PV患者中性粒细胞中的止血相关途径。整合数据集（GSE57793，GSE26049和GSE61629）的加权基因共表达网络分析（WGCNA）用于鉴定与PV中血栓形成相关的嗜中性粒细胞相关基因和途径。使用GSE47018数据集进行独创性途径分析(IPA)以鉴定有或没有血栓形成的PV患者中的差异激活途径。我们的数据显示PV患者的ANC增加。多因素logistic回归分析显示，ANC是PV患者诊断前或诊断时发生血栓事件的独立危险因素。ANC与PV患者的高凝状态相关。中性粒细胞胞外陷阱(NETs)通路在PV患者的中性粒细胞中显著富集。IPA结果表明，PRKCD介导的NETs通路在血栓形成的PV患者中过度激活。总之,ANC是诊断前或诊断时PV患者血栓形成事件的独立危险因素。PRKCD介导的NETs通路在PV患者的中性粒细胞中异常激活,并与血栓事件相关.
