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ST6Gal-I Predicts Postoperative Clinical Outcome for Patients with Localized Clear-cell Renal Cell Carcinoma

  • Liu, Hai-Ou (Key Laboratory of Glycoconjugate Research, MOH, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Shanghai Medical College of Fudan University) ;
  • Wu, Qian (Key Laboratory of Glycoconjugate Research, MOH, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Shanghai Medical College of Fudan University) ;
  • Liu, Wei-Si (Key Laboratory of Glycoconjugate Research, MOH, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Shanghai Medical College of Fudan University) ;
  • Liu, Yi-Dong (Key Laboratory of Glycoconjugate Research, MOH, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Shanghai Medical College of Fudan University) ;
  • Fu, Qiang (Key Laboratory of Glycoconjugate Research, MOH, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Shanghai Medical College of Fudan University) ;
  • Zhang, Wei-Juan (Department of Immunology, School of Basic Medical Sciences, Shanghai Medical College of Fudan University) ;
  • Xu, Le (Department of Urology, Zhongshan Hospital, Shanghai Medical College of Fudan University) ;
  • Xu, Jie-Jie (Key Laboratory of Glycoconjugate Research, MOH, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Shanghai Medical College of Fudan University)
  • Published : 2015.01.06

Abstract

Hyperactivated ${\alpha}2$-6-sialylation on N-glycans due to overexpression of the Golgi enzyme ${\beta}$-galactoside: ${\alpha}2$-6-sialyltransferase (ST6Gal-I) often correlates with cancer progression, metastasis, and poor prognosis. This study was aimed to determine the association between ST6Gal-I expression and the risk of recurrence and survival of patients with localized clear-cell renal cell carcinoma (ccRCC) following surgery. We retrospectively enrolled 391 patients (265 in training cohort and 126 in validation cohort) with localized ccRCC underwent nephrectomy at a single center. Tissue microarrays were constructed for immunostaining of ST6Gal-I. Prognostic value and clinical outcomes were evaluated. High ST6Gal-I expression was associated with Fuhrman grade (p<0.001 and p=0.016, respectively) and the University of California Los-Angeles Integrated Staging System (UISS) score (p=0.004 and p=0.017, respectively) in both cohorts. Patients with high ST6Gal-I expression had significantly worse overall survival (OS) (p<0.001 and p<0.001, respectively) and recurrence free survival (RFS) (p<0.001 and p=0.002, respectively) than those with low expression in both cohorts. On multivariate analysis, ST6Gal-I expression remained associated with OS and RFS even after adjusting for the UISS score. Stratified analysis suggested that the association is more pronounced among patients with low and intermediate-risk disease defined by the UISS score. High ST6Gal-I expression is a potential independent adverse predictor of survival and recurrence in ccRCC patients, and the prognostic value is most prominent in those with low and intermediate-risk disease defined by the UISS score.

Keywords

Clear-cell renal cell carcinoma;ST6Gal-I;prognostic biomarker;overall survival;recurrence free survival

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