Human plasma carboxylesterase 1, a novel serologic biomarker candidate for hepatocellular carcinoma |
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Authors: | Keun Na Eun‐Young Lee Hyoung‐Joo Lee Kwang‐Youl Kim Hanna Lee Seul‐Ki Jeong An‐Sung Jeong Sang Yun Cho Sun A Kim Si Young Song Kyung Sik Kim Sung Won Cho Hoguen Kim Young‐Ki Paik |
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Institution: | 1. Graduate Program in Functional Genomics, Yonsei Proteome Research Center and Biomedical Proteome Research Center, Yonsei University, Seoul, Korea;2. Department of Biochemistry, Yonsei Proteome Research Center and Biomedical Proteome Research Center, Yonsei University, Seoul, Korea;3. Department of Pathology, Yonsei University College of Medicine, Seoul, Korea;4. Department of Internal Medicine, Yonsei Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea;5. Department of Surgery, Yonsei University College of Medicine, Seoul, Korea;6. Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea |
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Abstract: | 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 N‐linked 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. |
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Keywords: | Biomarker Carboxylesterase 1 Glycoproteomics Hepatocellular carcinoma N‐linked glycoprotein |
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