Abstract:
The Finkel-Biskis-Jinkins Osteosarcoma (c-Fos; encoded by FOS) plays an important role in several cardiovascular diseases, including atherosclerosis and stroke. However, the relationship between FOS and venous thromboembolism (VTE) remains unknown. We identified differentially expressed genes in Gene Expression Omnibus dataset, GSE48000, comprising VTE patients and healthy individuals, and analysed them using CIBERSORT and weighted co-expression network analysis (WGCNA). FOS and CD46 expressions were significantly downregulated (FOS p = 2.26E-05, CD64 p = 8.83E-05) and strongly linked to neutrophil activity in VTE. We used GSE19151 and performed PCR to confirm that FOS and CD46 had diagnostic potential for VTE; however, only FOS showed differential expression by PCR and ELISA in whole blood samples. Moreover, we found that hsa-miR-144 which regulates FOS expression was significantly upregulated in VTE. Furthermore, FOS expression was significantly downregulated in neutrophils of VTE patients (p = 0.03). RNA sequencing performed on whole blood samples of VTE patients showed that FOS exerted its effects in VTE via the leptin-mediated adipokine signalling pathway. Our results suggest that FOS and related genes or proteins can outperform traditional clinical markers and may be used as diagnostic biomarkers for VTE.
摘要:
Finkel-Biskis-Jinkins骨肉瘤(c-Fos;由FOS编码)在几种心血管疾病中起着重要作用,包括动脉粥样硬化和中风.然而,FOS与静脉血栓栓塞(VTE)之间的关系尚不清楚.我们在基因表达综合数据集中鉴定了差异表达基因,GSE48000,包括VTE患者和健康个体,并使用CIBERSORT和加权共表达网络分析(WGCNA)对其进行了分析。FOS和CD46表达显着下调(FOSp=2.26E-05,CD64p=8.83E-05),并与VTE中的中性粒细胞活性密切相关。我们使用GSE19151并进行PCR以确认FOS和CD46具有诊断VTE的潜力;然而,只有FOS通过PCR和ELISA在全血样品中显示差异表达。此外,我们发现调节FOS表达的hsa-miR-144在VTE中显著上调.此外,VTE患者的中性粒细胞中FOS表达显著下调(p=0.03)。对VTE患者的全血样品进行的RNA测序表明,FOS通过瘦素介导的脂肪因子信号通路在VTE中发挥了作用。我们的结果表明,FOS和相关基因或蛋白质可以优于传统的临床标志物,并且可以用作VTE的诊断生物标志物。