Core 2 β-1, 6-N-acetylglucosaminyltransferase-1 expression in prostate biopsy specimen is an indicator of prostate cancer aggressiveness

Abstract

Introduction: To avoid over-treatment of early stage prostate cancer (PCa), predictive biomarkers for PCa aggressiveness which can be obtained during pre-treatment evaluation are essential. Core 2 β-1, 6-N-acetylglucosaminyl-transferase-1 (GCNT1) is a key enzyme that forms core 2 branched O-glycans, the expression of which is associated with aggressive potential of prostate cancer. We examined whether GCNT1 expression in prostate biopsy specimen can predict cancer recurrence after radical prostatectomy for the patients with with PCa. We then investigated molecular background for aggressive malignant potential mediated by GCNT1 expression.Methods: Paraffin-embedded PCa biopsy specimens were immunohisto-chemically tested for GCNT1 expression using an anti-GCNT1 monoclonal antibody. We also examined the role of GCNT1 in PCa progression using cell lines which express high or low levels of GCNT1.Results: GCNT1 expression correlated with D' Amico's recurrence risk classification. The GCNT1-positive rate in organ confined PCa was significantly lower than that in PCa with extra-prostatic extension. GCNT1-negative tumors were associated with significantly better prostate-specific antigen (PSA)-free survival compared with GCNT1-positive tumors. Multivariate analysis revealed that GCNT1 expression status was an independent risk factor for PSA recurrence after radical prostatectomy. Subsequent basic study revealed that GCNT1-over-expressing cells produced a significantly larger amount of growth factors when co-cultured with prostate stromal cells compared with GCNT1-knocked down cells and formed larger tumors. Conclusions: GCNT1 expression in prostate biopsy specimen is a significant and independent predictor of recurrence after radical prostatectomy, which can be used in pre-treatment decision making for the patient. Further validation study is necessary to establish clinical implication of GCNT1 in management of PCa.3

A Systematic Review on the Implications of O-linked Glycan Branching and Truncating Enzymes on Cancer Progression and Metastasis

“…Furthermore, O-glycan-terminated MUC1 reduces the adhesive characteristics of PCa cells [122]. When C2GnT-1-overexpressed PCa cells were injected into nude mice, it resulted in larger tumors compared to the vector control [123]. C2GnT1-expressing PCa cells possessed higher binding to prostate stromal cells and released significantly higher amounts of growth factors, such as HGF, FGF, and VEGFA.…”

Hepatitis B virus X protein influences enrichment profiles of H3K9me3 on promoter regions in human hepatoma cell lines

“…Study has found that GAPDH itself or GAPDH-related proteins may be involved in lung tumorigenesis [28]. The expression of GCNT1 has strong correlation with tumorigenicity, development and metastasis in human prostate cancers [29, 30]. Furthermore, recent study has identified that DNA methylation of the SLC16A3 promoter is involved in the regulation of monocarboxylate transporter 4 (MCT4) in renal cancer resulting in cell apoptosis [31].…”

Glycosylation is a global target for androgen control in prostate cancer cells

“…Role in synthesising the F77 antigen which increases prostate cancer cell growth . Correlates with aggressive disease (Kojima et al 2015) and is a predictor of recurrence after radical prostatectomy (Sato et al 2016). Detected in patient urine (Kojima et al 2015).…”

“…Our analysis of the prostate cancer transcriptome also identified the core 2 branching enzyme GCNT1 as an AR target gene in prostate cancer patients . GCNT1 is upregulated in prostate cancer in which its expression correlates with aggressive disease and is a predictor of recurrence after radical prostatectomy (Hagisawa et al 2005, Kojima et al 2015, Sato et al 2016. GCNT1 can be detected in patient urine where in combination with PSA it is a reliable indicator for extracapsular extension of prostate cancer (Kojima et al 2015).…”