Soe Hui Jen, Yong Yean K, Al-Obaidi Mazen M Jamil, Raju Chandramathi Samudi, Gudimella Ranganath, Manikam Rishya, Sekaran Shamala Devi
Department of Medical Microbiology Department of Trauma and Emergency, Faculty of Medicine, University of Malaya Laboratory Centre, Xiamen University Malaysia, China-ASEAN College of Marine Biotechnology, Sepang, Selangor Faculty of Medicine, MAHSA University, Bandar Saujana Putra Sengenics Corporation, HIR Building, University Malaya 50603 Kuala Lumpur, Malaysia.
Medicine (Baltimore). 2018 Feb;97(5):e9713. doi: 10.1097/MD.0000000000009713.
Dengue virus is one of the most widespread flaviviruses that re-emerged throughout recent decades. The progression from mild dengue to severe dengue (SD) with the complications such as vascular leakage and hemorrhage increases the fatality rate of dengue. The pathophysiology of SD is not entirely clear. To investigate potential biomarkers that are suggestive of pathogenesis of SD, a small panel of serum samples selected from 1 healthy individual, 2 dengue patients without warning signs (DWS-), 2 dengue patients with warning signs (DWS+), and 5 patients with SD were subjected to a pilot analysis using Sengenics Immunome protein array. The overall fold changes of protein expressions and clustering heat map revealed that PFKFB4, TPM1, PDCL3, and PTPN20A were elevated among patients with SD. Differential expression analysis identified that 29 proteins were differentially elevated greater than 2-fold in SD groups than DWS- and DWS+. From the 29 candidate proteins, pathways enrichment analysis also identified insulin signaling and cytoskeleton pathways were involved in SD, suggesting that the insulin pathway may play a pivotal role in the pathogenesis of SD.
登革病毒是近几十年来再度出现的传播最为广泛的黄病毒之一。从轻度登革热发展为伴有血管渗漏和出血等并发症的重症登革热(SD)会增加登革热的死亡率。SD的病理生理学尚不完全清楚。为了研究提示SD发病机制的潜在生物标志物,从1名健康个体、2名无警示体征的登革热患者(DWS-)、2名有警示体征的登革热患者(DWS+)和5名SD患者中选取了一小批血清样本,使用Sengenics免疫组蛋白阵列进行了初步分析。蛋白质表达的总体倍数变化和聚类热图显示,SD患者中磷酸果糖激酶-2B4(PFKFB4)、原肌球蛋白1(TPM1)、程序性死亡配体3(PDCL3)和蛋白酪氨酸磷酸酶非受体型20A(PTPN20A)升高。差异表达分析确定,与DWS-和DWS+相比,SD组中有29种蛋白质差异升高超过2倍。在这29种候选蛋白质中,通路富集分析还确定胰岛素信号通路和细胞骨架通路与SD有关,这表明胰岛素通路可能在SD的发病机制中起关键作用。