title: Overexpression of O-GlcNAc by prostate cancer cells is significantly associated with poor prognosis of patients.
abstract: BACKGROUND
  O-linked β-N-acetylglucosamine (O-GlcNAc) is a glycan essential for fundamental cellular processes such as transcription/translation, nuclear transport, protein stability and protein-protein interactions. However, the role of O-GlcNAc in prostate cancer progression of patients remains poorly unknown. Here we investigated the clinicopathological significance of O-GlcNAc expression level in prostate cancer.
  
  
  METHODS
  O-GlcNAc expression level in prostate cancer cells was determined by immunohistochemistry of prostate biopsy specimens obtained from 56 patients later treated with hormone deprivation therapy comparing with adjacent normal prostate glands in the same sections. Overall survival was determined by the Kaplan-Meier and Cox proportional hazards methods with univariate and multivariate models. The effects of reduced O-GlcNAc expression level on proliferation and invasion of prostate cancer LNCaP cells were examined using small interfering RNA (siRNA) targeting O-GlcNAc transferase (OGT), the enzyme responsible for O-GlcNAc biosynthesis.
  
  
  RESULTS
  Defining cancer cells showing stronger cytoplasmic staining than normal prostate glands as overexpression of O-GlcNAc, 39% of prostate cancer patients were categorized as overexpression. The Kaplan-Meier and Cox proportional hazards methods with univariate model analysis revealed that O-GlcNAc overexpression was associated with overall survival (P=0.0012 for the Kaplan-Meier and P=0.0021 for Cox univariate hazard model analysis). Furthermore, O-GlcNAc was the only item in which a significant difference was observed at overall survival by multivariate analysis (P=0.0475). Finally, siRNA-mediated OGT knockdown in LNCaP cells resulted in decreased expression of O-GlcNAc and promoted decreased proliferation and tumor cell invasion compared with control siRNA-transfected LNCaP cells.
  
  
  CONCLUSIONS
  These results indicate that O-GlcNAc expression level in prostate cancer cells is associated with poor prognosis of prostate cancer patients and likely enhances tumor cell proliferation and invasion.
authors.affiliation: 1] Department of Urology, Shinshu University School of Medicine, Matsumoto, Japan [2] Department of Molecular Pathology, Shinshu University Graduate School of Medicine, Matsumoto, Japan [3] Department of Urology, Nagano Municipal Hospital, Nagano, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kamigaito
authors.affiliation: Department of Urology, Nagano Municipal Hospital, Nagano, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Okaneya
authors.affiliation: Department of Molecular Pathology, Shinshu University Graduate School of Medicine, Matsumoto, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kawakubo
authors.affiliation: Department of Pathology, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Shimojo
authors.affiliation: Department of Urology, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: O
authors.initials: O
authors.lastname: Nishizawa
authors.affiliation: Department of Molecular Pathology, Shinshu University Graduate School of Medicine, Matsumoto, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Nakayama
mesh_terms: D000117:Acetylglucosamine / Q000378:metabolism*; D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D055785:Gene Knockdown Techniques; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics / Q000378:metabolism; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology
chemical_list: D017351:N-Acetylglucosaminyltransferases; C449880:O-GlcNAc transferase; D000117:Acetylglucosamine