Up-regulation of annexin A2 in cholangiocarcinoma caused by Opisthorchis viverrini and its implication as a prognostic marker.

Up-regulation of annexin A2 in cholangiocarcinoma caused by Opisthorchis viverrini and its implication as a prognostic marker.
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DOI:
10.1016/j.ijpara.2010.05.002
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发表时间:
2010-08-15
影响因子:
4
通讯作者:
Sripa B
Sripa B
中科院分区:
医学2区
文献类型:
--
作者:
Yonglitthipagon P;Pairojkul C;Chamgramol Y;Mulvenna J;Sripa B

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胆管癌(CCA),或胆管癌,在泰国东北部主要与肝吸虫感染有关。疾病。与晚期发病有关,给诊断带来挑战,死亡率高——这些特征突出了对肿瘤标志物的需求。目前还没有特异性的肿瘤标志物可以指示CCA的早期阶段和状态。对肿瘤细胞表面表达的蛋白质进行蛋白质组学分析尤其困难,因为迄今为止,由于缺乏有效的疏水膜蛋白分析策略,对表面膜蛋白进行蛋白质组学分析受到阻碍。在本研究中,利用序列蛋白提取来克服这一问题。从4种不同肿瘤形成能力的CCA细胞系中提取膜蛋白。非肿瘤H69胆道细胞系作为对照。采用二维page和MALDI-TOF-MS对差异表达蛋白进行鉴定。在CCA细胞系中发现的20个上调膜蛋白中,ANXA2参与了其他肿瘤的侵袭和转移。因此,通过使用商业抗小鼠单克隆抗体和组织微阵列CCA(301例确诊病例)探测,在人类受试者中验证了ANXA2,发现它与淋巴侵袭(P = 0.014)和转移(P = 0.026)所反映的几种肿瘤进展阶段之一有关。高表达ANXA2的患者生存期明显缩短(P = 0.011)。肿瘤中ANXA2的表达可能有助于预测CCA患者的不良预后。
Cholangiocarcinoma (CCA), or cancer of the bile ducts, is primarily associated with infection with the liver fluke Opisthorchis viverrini in northeast Thailand. The disease . is associated with late presentation, poses challenges for diagnosis and has a high mortality rate – features that highlight the need for tumor markers. At present, there are no specific tumor markers that can indicate the early stages and status of CCA. Proteomic analysis of the proteins expressed on the surface of tumor cells is particularly difficult since proteome-wide analysis of surface membrane proteins has thus far been hampered by the lack of effective strategies to profile hydrophobic membrane proteins. In this study, a sequential protein extraction was utilized to overcome this problem. Membrane protein was extracted from four CCA cell lines with different tumor forming capabilities. The non-tumor H69 biliary cell line was used as a control. Two-dimensional-PAGE followed by MALDI-TOF-MS was used to identify differentially expressed proteins. Among 20 up-regulated membrane proteins identified in the CCA cell lines was ANXA2, a participant in tumor invasion and metastasis in other cancers. Accordingly, ANXA2 was verified in human subjects by probing, using a commercial anti-mouse monoclonal antibody and a tissue microarray of CCA (301 diagnosed cases), where it was found to associate with one of several tumor progression stages as reflected by lymphatic invasion (P = 0.014) and metastasis (P = 0.026). Patients with high expression of ANXA2 had a significantly shorter survival time (P = 0.011). ANXA2 expression in tumors may be useful for predicting the poor outcome of CCA patients.
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