title: Core 2 β-1, 6-N-acetylglucosaminyltransferase-1 expression in prostate biopsy specimen is an indicator of prostate cancer aggressiveness.
abstract: BACKGROUND
  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.
authors.affiliation: Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors.forename: Tendo
authors.initials: T
authors.lastname: Sato
authors.affiliation: Department of Advanced Transplant and Regenerative Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Yoneyama
authors.affiliation: Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan; Hirosaki University Graduate School of Medicine, Hirosaki, Japan. Electronic address: tobisawa@hirosaki-u.ac.jp.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Tobisawa
authors.affiliation: Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Hatakeyama
authors.affiliation: Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors.forename: Hayato
authors.initials: H
authors.lastname: Yamamoto
authors.affiliation: Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Kojima
authors.affiliation: Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors.forename: Jotaro
authors.initials: J
authors.lastname: Mikami
authors.affiliation: Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Mori
authors.affiliation: Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Hashimoto
authors.affiliation: Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Koie
authors.affiliation: Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan; Department of Advanced Transplant and Regenerative Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors.forename: Chikara
authors.initials: C
authors.lastname: Ohyama
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018572:Disease-Free Survival; D006801:Humans; D015994:Incidence; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D017351:N-Acetylglucosaminyltransferases / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000201:enzymology* / Q000453:epidemiology / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000453:epidemiology / Q000473:pathology*; D015203:Reproducibility of Results; D012307:Risk Factors; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; D017351:N-Acetylglucosaminyltransferases; C053024:beta-1,3-galactosyl-O-glycosyl-glycoprotein beta-1,6-acetylglucosaminyl transferase
keywords: 6-N-Acetylglucosaminyltransferase-1; Core 2 β-1; Cytokines; Prostate cancer; Radical prostatectomy