Human plasma carboxylesterase 1, a novel serologic biomarker candidate for hepatocellular carcinoma
Human plasma carboxylesterase 1, a novel serologic biomarker candidate for hepatocellular carcinoma
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DOI：
10.1002/pmic.200900105
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发表时间：
2009-08-01
期刊：
影响因子：
3.4
通讯作者：
Paik, Young-Ki
中科院分区：
文献类型：
--
作者：
Na, Keun;Lee, Eun-Young;Paik, Young-Ki
为鉴定和鉴定肝细胞癌的血清学糖蛋白生物标志物，采用多重凝集素亲和层析技术从5组配对的非肿瘤组织和肿瘤组织中分离细胞内N-连接糖蛋白部分。从2-D DGE靶向差异表达的眨眼糖蛋白序列中，我们鉴定了在肿瘤组织中显著下调的人肝羧酸酯酶1(HCE1)，这一发现得到了来自58例肝癌患者的非肿瘤组织和肿瘤组织的Western印迹、实时定量RT-PCR和免疫组织化学染色的证实。为了研究hCE1是否也存在于人血浆中，我们采用了基于磁珠的免疫沉淀和纳米LC-MS/MS分析，我们首次发现hCE1存在于人血浆中，而不是肝组织中。也就是说，从免疫沉淀和Western印迹分析hCE1信号的正常化来看，肝细胞癌患者的血浆标本中的hCE1水平高于其他疾病组(如肝硬变、慢性肝炎、胆管细胞癌、胃癌和胰腺癌)的血浆中的hCE1水平。肝细胞癌受试者操作特征分析的敏感性和特异性均大于70.0%和85.0%。因此，高分辨率蛋白质组学方法表明，hCE1是一个很好的候选者，可以进一步验证为肝癌的血清学糖蛋白生物标记物。
To identify and characterize a serologic glycoprotein biomarker for hepatocellular carcinoma (HCC), multi-lectin affinity chromatography was used to isolate intracellular N-linked glycoprotein fractions from five paired non-tumor and tumor tissues. From the series of 2-D DIGE targeted differentially expressed Winked glycoproteins, we identified human liver carboxylesterase 1 (hCE1), which was remarkably down-regulated in tumor tissues, a finding confirmed by Western blot, a quantitative real-time RT-PCR, and immunohistochemical staining of non-tumor and tumor tissues from total 58 HCC patients. To investigate whether hCE1 is also present in human plasma, we employed a magnetic bead-based immunoprecipitation followed by nano-LC-MS/MS analysis, and we found for the first time that hCE1 is present in human plasma as opposed to that in liver tissues. That is, from normalization of hCE1 signal by the immunoprecipitation and Western blot analysis, hCE1 levels were increased in plasma specimens from HCC patients than in plasma from other disease patient groups (e.g. liver cirrhosis, chronic hepatitis, cholangiocarcinoma, stomach cancer, and pancreatic cancer). From the receiver operating characteristic analysis in HCC, both sensitivity and specificity were shown to be greater than 70.0 and 85.0%, respectively. Thus, the high-resolution proteomic approach demonstrates that hCE1 is a good candidate for further validation as a serologic glycoprotein biomarker for HCC.