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β1,6-N-acetylglucosaminyltransferase V predicts recurrence and survival of patients with clear-cell renal cell carcinoma after surgical resection

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Abstract

Purpose

β1,6-N-acetylglucosaminyltransferase V (MGAT5), which is required for the biosynthesis of β1,6GlcNAc-branched N-linked glycans attached to cell surface and secreted glycoproteins, accounts for oncogenic growth signal transduction during the development and progression of various malignancies. Our present study aimed to evaluate the impact of MGAT5 expression on recurrence and survival of patients with clear-cell renal cell carcinoma (ccRCC) following surgery.

Methods

We retrospectively enrolled 265 patients (196 in the training cohort and 69 in the validation cohort) with ccRCC undergoing nephrectomy at a single institution. Clinicopathologic features, overall survival (OS) and recurrence-free survival (RFS) were recorded. MGAT5 intensities were assessed by immunohistochemistry in specimens of patients. Kaplan–Meier method was applied to compare survival curves. Cox regression models were used to analyze the impact of prognostic factors on OS and RFS. Concordance index (C-index) was calculated to assess predictive accuracy.

Results

In both cohorts, MGAT5 expression positively correlated with metastatic and advanced TNM stage. High MGAT5 expression indicated poor survival (P < 0.001 in training set and P < 0.001 in validation set) and early recurrence (P < 0.001 in training set and P = 0.004 in validation set) of patients with ccRCC. After multivariate Cox regression analysis, MGAT5 expression was identified as an independent adverse prognostic factor for survival and recurrence. The predictive accuracy of TNM, UISS and SSIGN prognostic models was improved when MGAT5 expression was added.

Conclusions

MGAT5 expression is a potential independent adverse prognostic biomarker for recurrence and survival of patients with ccRCC after nephrectomy.

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Acknowledgments

We thank Ms. Haiying Zeng (Department of Pathology, Zhongshan Hospital, Shanghai Medical College of Fudan University) for technical assistance. This work was supported by grants from the National Basic Research Program of China (2012CB822104 to J. X.), the National Key Projects for Infectious Diseases of China (2012ZX10002-012 to J. X.), the National Natural Science Foundation of China (31100629 and 81471621 to W. Z., 31270863 and 81472227 to J. X.), the Program for New Century Excellent Talents in University (NCET-13-0146 to J. X.) and the Shanghai Rising-Star Program (13QA1400300 to J. X.).

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical standard

The study was approved by the research medical ethics committee of Fudan University, and informed consent was provided by each patient.

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Author notes

    Authors and Affiliations

    1. Key Laboratory of Glycoconjugate Research, MOH, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Shanghai Medical College of Fudan University, Mailbox 103, 138 Yixueyuan Road, Shanghai, 200032, China

      Yidong Liu, Haiou Liu, Weisi Liu & Jiejie Xu

    2. Department of Immunology, School of Basic Medical Sciences, Shanghai Medical College of Fudan University, Shanghai, 200032, China

      Weijuan Zhang

    3. Department of Urology, Zhongshan Hospital, Shanghai Medical College of Fudan University, Shanghai, 200032, China

      Huimin An

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    1. Yidong Liu
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    Correspondence to Jiejie Xu.

    Additional information

    Yidong Liu, Haiou Liu and Weisi Liu have contributed equally to this work.

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    345_2014_1451_MOESM1_ESM.tif

    Supplementary material 1 β1,6-N-acetylglucosaminyltransferase V (MGAT5) expression in clear-cell renal cell carcinoma (ccRCC) tissues. (a) Representative MGAT5 immunohistochemical (IHC) images of ccRCC tumor tissues. Arrows indicate positive staining of MGAT5 in each image (original magnification x 200). Scale bar: 50 μm. (b) The patient percentage of high MGAT5 density in localized ccRCC patients and metastatic ccRCC patients in training set (n=187, n=9, respectively) and validation set (n=62, n=7, respectively) (TIFF 7437 kb)

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    Liu, Y., Liu, H., Liu, W. et al. β1,6-N-acetylglucosaminyltransferase V predicts recurrence and survival of patients with clear-cell renal cell carcinoma after surgical resection. World J Urol 33, 1791–1799 (2015). https://doi.org/10.1007/s00345-014-1451-x

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    • DOI: https://doi.org/10.1007/s00345-014-1451-x

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