Wang Dehao, Zhao Pei, Lv Yan, Ming Jing, Wang Ziqing, Yang Erpeng, Li Yumeng, Wang Mingjing, Niu Jicong, Zhang Yanyu, Sun Yan, Chen Yi, Chen Ke, Chen Zhuo, Liu Weiyi, Hu Xiaomei
Graduate School, Beijing University of Chinese Medicine, Beijing 100029, China.
Department of Hematology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China.
J Clin Med. 2023 Jan 30;12(3):1078. doi: 10.3390/jcm12031078.
Abnormal platelet activation can lead to thrombosis in essential thrombocythemia (ET) and thus impact patient prognosis. Platelet activation-associated proteins are key molecules for platelet activation. However, it is unclear which proteins are most closely associated with the disease's prognosis. To determine which platelet activation-related proteins can be employed as ET patient prognosis predictors, we used label-free quantification (LFQ) and parallel reaction monitoring (PRM) technology and first determined the serum proteomic expression levels and the differential proteins of ET patients. Then, based on the IPSET (International Prognostic Score for ET), the differential protein associated with the prognostic score was found. To investigate potential processes affecting prognosis, the connection of this protein with prognostic markers, such as thrombotic history, age, white blood cell count, coagulation factors, and inflammatory factors, were further examined. The levels of platelet activation-related proteins GPIbα, SELP, PF4, MMP1, and FLNA were significantly higher in ET patients, according to LFQ and PRM analyses ( < 0.01). Based on regression analysis of the IPSET prognostic score, it is suggested that the SELP level was positively correlated with the prognostic score and prognostic risk factor analysis ( < 0.05). Further regression analysis of SELP with coagulation factors showed that antithrombin (AT-III) was negatively correlated with SELP levels ( < 0.05). Further regression analysis of the inflammatory factors with AT-III and SELP revealed that IL-10, IL-12P70, and IL-31 were negatively correlated with AT-III and SELP ( < 0.01). Platelet activation pathway-related proteins are expressed more frequently in ET patients, and serum SELP may be a prognostic marker for these individuals by encouraging leukocyte increase and inflammatory factor expression and causing aberrant coagulation.
异常的血小板激活可导致原发性血小板增多症（ET）中的血栓形成，从而影响患者预后。血小板激活相关蛋白是血小板激活的关键分子。然而，尚不清楚哪些蛋白与该疾病的预后最为密切相关。为了确定哪些血小板激活相关蛋白可作为ET患者预后的预测指标，我们使用了无标记定量（LFQ）和平行反应监测（PRM）技术，首先确定了ET患者的血清蛋白质组表达水平和差异蛋白。然后，基于IPSET（ET国际预后评分），发现了与预后评分相关的差异蛋白。为了研究影响预后的潜在过程，进一步检查了该蛋白与血栓形成病史、年龄、白细胞计数、凝血因子和炎症因子等预后标志物的关联。根据LFQ和PRM分析，ET患者中血小板激活相关蛋白GPIbα、SELP、PF4、MMP1和FLNA的水平显著更高（<0.01）。基于IPSET预后评分的回归分析，提示SELP水平与预后评分呈正相关，且预后危险因素分析（<0.05）。SELP与凝血因子的进一步回归分析表明，抗凝血酶（AT-III）与SELP水平呈负相关（<0.05）。AT-III和SELP与炎症因子的进一步回归分析显示，IL-10、IL-12P70和IL-31与AT-III和SELP呈负相关（<0.01）。血小板激活途径相关蛋白在ET患者中表达更频繁，血清SELP可能通过促进白细胞增加和炎症因子表达以及导致异常凝血，成为这些个体的预后标志物。
