title: ST6Gal-I predicts postoperative clinical outcome for patients with localized clear-cell renal cell carcinoma.
abstract: Hyperactivated α2-6-sialylation on N-glycans due to overexpression of the Golgi enzyme β-galactoside: α2-6- 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.
authors.affiliation: Key Laboratory of Glycoconjugate Research, MOH, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Shanghai Medical College of Fudan University, Shanghai, China E-mail : jjxufdu@fudan.edu.cn.
authors.forename: Hai-Ou
authors.initials: HO
authors.lastname: Liu
authors.forename: Qian
authors.initials: Q
authors.lastname: Wu
authors.forename: Wei-Si
authors.initials: WS
authors.lastname: Liu
authors.forename: Yi-Dong
authors.initials: YD
authors.lastname: Liu
authors.forename: Qiang
authors.initials: Q
authors.lastname: Fu
authors.forename: Wei-Juan
authors.initials: WJ
authors.lastname: Zhang
authors.forename: Le
authors.initials: L
authors.lastname: Xu
authors.forename: Jie-Jie
authors.initials: JJ
authors.lastname: Xu
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009392:Nephrectomy; D011379:Prognosis; D012189:Retrospective Studies; D012799:Sialyltransferases / Q000378:metabolism*; D016896:Treatment Outcome; D047368:Tumor Burden; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase
chemical_list: D015703:Antigens, CD; D012799:Sialyltransferases; C093493:ST6GAL1 protein, human; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase