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.
Highlights
Renal cell carcinoma (RCC) accounts for approximately 90% of all kidney malignancies, and 85% of RCC are clear cell types (Motzer et al, 2009)
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 following surgery
Stratified analysis suggested that the association is more pronounced among patients with low and intermediate-risk disease defined by the University of California Los-Angeles Integrated Staging System (UISS) score
Summary
Renal cell carcinoma (RCC) accounts for approximately 90% of all kidney malignancies, and 85% of RCC are clear cell types (Motzer et al, 2009). These commonly mutated genes, VHL, PBRM1, SETD2 and BRAP1, could have far-reaching effects on metabolic shift, involving downregulation of genes involved in the TCA cycle, upregulation of the pentose phosphate pathway and the glutamine transporter genes (Network, 2013). By altering their metabolism to favour aerobic glycolysis over lipid oxidation (a cancer phenomenon termed the “Warburg effect”) give rise to ccRCC progression (Preston et al, 2011; Li et al, 2014). Accumulating evidences indicate that higher intratumor expression levels of ST6Gal-I are indicator of
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