Identification of potential pancreatic cancer serum markers: Increased sialyl-Lewis X on ceruloplasmin
Identification of potential pancreatic cancer serum markers: Increased sialyl-Lewis X on ceruloplasmin
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DOI：
10.1016/j.cca.2015.01.007
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发表时间：
2015-03-10
影响因子：
5
通讯作者：
Peracaula, Rosa
中科院分区：
文献类型：
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作者：
Balmana, Meritxell;Sarrats, Ariadna;Peracaula, Rosa
胰腺癌(PDAC)通常表现为唾液酸化-刘易斯X(SLE(X))及其相关表位的表达增强。PDAC可以分泌一些携带这种增加的SLE(X)决定簇的蛋白质进入血清，因此它们可以作为PDAC的标志物。此前，我们在PDAC和慢性胰腺炎患者中都发现了SLE(X)升高的急性期蛋白。在这项研究中，分析了主要急性期蛋白的耗尽血清，以寻找PDAC中SLE(X)水平升高的蛋白。取健康对照组、慢性胰腺炎和PDAC患者的血清，进行SLE(X)免疫检测。对PDAC中差异表达的SLE(X)蛋白进行分型消化，并用LC-ESI-QTOF质谱仪进行鉴定。在PDAC中鉴定出5条差异表达SLE(X)的蛋白条带，分别对应于7个不同的急性时相蛋白。其中，铜蓝蛋白(CP)被选作进一步分析。CP的N-葡聚糖序列测定证实了PDAC患者CP中SLE(X)水平的升高。用抗CP抗体免疫沉淀正常人、慢性胰腺炎和PDAC患者血清，用免疫印迹法检测其SLE(X)和CP水平。SLE(X)/Cp比值在PDAC组有较高的趋势，提示SLE(X)/Cp比值可作为PDAC的有用生物标志物。(C)2015爱思唯尔B.V.保留所有权利。
Pancreatic adenocarcinoma (PDAC) usually shows an enhanced expression of sialyl-Lewis X (sLe(x)) and related epitopes. PDAC may secrete some of the proteins carrying such increased sLe(x) determinant into serum, so they could be used as PDAC markers. Previously, we identified acute-phase proteins with increased sLe(x) in both PDAC and in chronic pancreatitis patients. In this study, depleted sera from the main acute-phase proteins has been analysed for the search of proteins with increased sLe(x) levels in PDAC. Sera from healthy controls, chronic pancreatitis and PDAC patients were depleted, electrophoresed and subjected to sLe(x) immunodetection. Proteins that differentially expressed sLe(x) in PDAC were typsin digested and identified by LC-ESI-QTOF mass spectrometry. Five protein bands that differentially expressed sLe(x) in PDAC were identified and corresponded to seven different acute-phase proteins. Among them, ceruloplasmin (CP) was selected for further analysis. N-glycan sequencing of CP confirmed the increase of sLe(x) levels in CP in PDAC patients. Healthy controls, chronic pancreatitis and PDAC patients' sera were immunoprecipitated with anti-CP antibodies, and their sLe(x) and CP levels were analysed by western blot. The sLe(x)/CP ratio tended to be higher for the PDAC group, which altogether suggests that the sLe(x)/CP ratio could be a useful biomarker for PDAC. (C) 2015 Elsevier B.V. All rights reserved.