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Multiple lectin assays for detecting glyco-alteration of serum GP73 in liver diseases

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Abstract

Serum GP73 is a functional resident Golgi type II membrane protein with three potential N-glycosylation sites. In this study, we used multiple lectin assays to analyze glycan patterns of serum GP73 and evaluated its diagnostic value for distinguishing hepatocellular carcinoma (HCC) from liver cirrhosis (LC). Firstly, Antibody overlay lectin microarray and lectin blot were performed to observe altered glycans of GP73. Fucosylated structures were found to increase significantly in LC compared with HCC patients. Then, AAL ELISA assay using ELISA Index was utilized to measure fucosylation level of GP73 on its protein level (Fuc-GP73). ELISA Indices of 54 LC and 54 HCC patients was obtained and the area under the ROC curve (AUC) was 0.807 with a sensitivity of 85.2 % and a specificity of 63.0 % (cutoff of 3.182). In addition, combining Fuc-GP73 and AFP-L3 greatly improved the diagnostic accuracy (AUC = 0.953) and the diagnostic values were 94.4 % sensitivity at 88.9 % specificity. These data indicated that multiple lectin assays could contribute to pre-clinical evaluation of focused glycoprotein and Fuc-GP73 could act as a potential glycobiomarker complementary to AFP-L3 for discrimination of HCC from LC patients.

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Acknowledgments

This work was financially supported by National High Tech Program (863 program: 2012AA020204), National Basic Research Program of China (973 Program: 2011CB910604), China National Key Projects for Infectious Diseases (2012ZX10002009-002, 2012ZX10002009-007 and 2012ZX10002012-002) and Open Fund of Key Laboratory of Glycoconjugate Research, Fudan University, Ministry of Public Health.

Author contributions

Y.L. K.G. and S.Z. conceived the idea. K.J., S.Z., S.S. and W.L performed the experiments, X.Q. supplied the sera specimens, K.J. and S.Z. analyzed the data, S.Z. wrote the manuscript.

Competing financial interests

The authors declare no competing financial interests.

Compliance with ethical standards

The serum specimens were obtained from the First Affiliated Hospital of Guangxi Medical University. This study was approved by the Research Ethics committee of First Affiliated Hospital of Guangxi Medical University and the Institutional Review Board of the National Cancer Center. Informed consent was obtained from each patient.

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Authors and Affiliations

  1. Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, 200032, China

    Kun Guo, Shu Zhang & Yinkun Liu

  2. Cancer Research Center, Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China

    Kai Jiang, Wei Li & Yinkun Liu

  3. Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi, China

    Shuxin Shang & Xue Qin

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  1. Kai Jiang
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  2. Shuxin Shang
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  3. Wei Li
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  6. Shu Zhang
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Correspondence to Shu Zhang.

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Jiang, K., Shang, S., Li, W. et al. Multiple lectin assays for detecting glyco-alteration of serum GP73 in liver diseases. Glycoconj J 32, 657–664 (2015). https://doi.org/10.1007/s10719-015-9614-6

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