A new glyco-biomarker for comprehensive evaluation of malignant potential in prostate cancer

• Project/Area Number: 24659708
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Urology
• Research Institution: Hirosaki University
• Principal Investigator: OHYAMA Chikara 弘前大学, 医学(系)研究科(研究院), 教授 (80282135)
• Co-Investigator(Kenkyū-buntansha): HATAKEYAMA Shingo 弘前大学, 医学研究科, 助教 (10400136) ; TSUBOI Shigeru 弘前大学, 医学研究科, 研究員 (20526727) ; MORI Kazuyuki 弘前大学, 医学研究科, 助教 (40266903) ; YONEYAMA Tohru 弘前大学, 医学研究科, 助教 (50587649) ; KOIE Takuya 弘前大学, 医学部附属病院, 講師 (60321965)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
• Keywords: 前立腺癌 / バイオマーカー / 悪性度診断法 / 糖タンパク / 1前立腺癌 / 再発予測

Outline of Final Research Achievements

We newly established　a　monoclonal　antibody　against　core2　beta1,6-N-acetylglucosaminyltransferase(C2GnT).Using　this　monoclonal antibpdy, we immunohinstochemically evaluated relationship between C2GnT expression and biochemical recurrence of prostate cancer after radical prostatectomy.　C2GnT exprsssion was a significant and independent predictor of biochemical recurrence.　　We then developed a new assay system for C2GnT using post prostate massage urine sample by dot-blot method. C2GnT expression in urine sample detedced by this new assay system was a sinigicant and independent predictor for capsular invasion in prostate cancer. We now on our way to examine the potential of urine C2GnT expression as a predictor for PSA recurrence after radical prostatectomy.
Further validation study is warranted.

Research Products

• [Journal Article] Serum N-glycan alteration associated with renal cell carcinoma detected by high-throughput glycan analysis. (2014)
  • Author(s): Hatakeyama S, Amano M, Tobisawa Y, Yoneyama T, Tsuchiya N, Habuchi T, Nishimura SI, Ohyama C
  • Journal Title: J Urol. Volume: 191 Issue: 3 Pages: 805-813
  • DOI: 10.1016/j.juro.2013.10.052
  • Peer Reviewed / Open Access
• [Journal Article] Serum tri-and tetra-antennary N-glycan is a potential predictive biomarker for castration-resistant prostate cancer. (2014)
  • Author(s): Ishibashi Y, Tobisawa Y, Hatakeyama S, Ohashi T, Tanaka M, Narita S, Koie T, Habuchi T, Nishimura S, Ohyama C, Yoneyama T
  • Journal Title: Prostate Volume: 74 Issue: 15 Pages: 1521-1529
  • DOI: 10.1002/pros.22869
  • Peer Reviewed / Open Access
• [Journal Article] Measurement of aberrant glycosylation of prostate specific antigen can improve specificity in early detection of prostate cancer. (2014)
  • Author(s): Yoneyama T, Ohyama C, Hatakeyama S, Narita S, Habuchi T, Koie T, Mori K, Hidari KI, Yamaguchi M, Suzuki T, Tobisawa Y
  • Journal Title: Biochem Biophys Res Commun. Volume: 448 Issue: 4 Pages: 390-396
  • DOI: 10.1016/j.bbrc.2014.04.107
  • Peer Reviewed / Open Access
• [Journal Article] Core2 O-glycan-expressing prostate cancer cells are resistant to NK cell immunity. (2013)
  • Author(s): Okamoto T，Yoneyama MS，Hatakeyama S，Mori K，Yamamoto H，Koie T，Saitoh H，Yamaya K，Funyu T，Fukuda M，Ohyama C，Tsuboi S
  • Journal Title: Mol Med Rep Volume: 7 Pages: 359-364
  • Peer Reviewed
• [Presentation] Laminin binding glycan depletion on α-dystroglycan in prostate cancer cells promotes epithelial-mesenchymal transition and enhances tumor formation. (2014)
  • Author(s): Yoneyama T, Hatakeyama S, Tobisawa Y, Koie T, Ohyama C, Fukuda M
  • Organizer: 第109回米国泌尿器学会議（AUA 2014）
  • Place of Presentation: オーランド
  • Year and Date: 2014-05-16 – 2014-05-21
• [Presentation] Measurement of Prostate Cancer-Associated Aberrant Glycosylation of Prostate Specific Antigen can improve diagnostic accuracy. (2014)
  • Author(s): Yoneyama T, Tobisawa Y, Hatakeyama S, Narita S, Habuchi T, Mori K, Koie T, Ohyama C
  • Organizer: 第109回米国泌尿器学会議（AUA 2014）
  • Place of Presentation: オーランド
  • Year and Date: 2014-05-16 – 2014-05-21
• [Presentation] Glycan modification of podoplanin enhances growth factor production through stabilization of platelet aggregation in bladder cancer cell. (2014)
  • Author(s): Tobisawa Y, Yoneyama T, Hatakeyama S, Yamamoto H, Okamoto T, Imai A, Yoneyama T, Hashimoto Y, Koie T, Ohyama C
  • Organizer: 第109回米国泌尿器学会議（AUA 2014）
  • Place of Presentation: オーランド
  • Year and Date: 2014-05-16 – 2014-05-21
• [Presentation] Detection of core2 -1,6-N-acetylglucosaminyltransferase in post-digital rectal examination urine is an independent predictor for extraprostatic extension of prostate cancer. (2014)
  • Author(s): Tobisawa Y, Yoneyama T, Hatakeyama S, Yamamoto H, Okamoto T, Imai A, Yoneyama T, Hashimoto Y, Koie T, Ohyama C
  • Organizer: 第109回米国泌尿器学会議（AUA 2014）
  • Place of Presentation: オーランド
  • Year and Date: 2014-05-16 – 2014-05-21
• [Presentation] Expression of I blood group antigen synthase correlates with malignant potential in prostate cancer. (2014)
  • Author(s): Tobisawa Y, Yoneyama T, Hatakeyama S, Yamamoto H, Okamoto T, Imai A, Yoneyama T, Hashimoto Y, Koie T, Ohyama C
  • Organizer: 第109回米国泌尿器学会議（AUA 2014）
  • Place of Presentation: オーランド
  • Year and Date: 2014-05-16 – 2014-05-21
• [Presentation] Measurement of Prostate Cancer-Associated Aberrant Glycosylation of Prostate Specific Antigen can improve diagnostic accuracy. (2014)
  • Author(s): Yoneyama T, Tobisawa Y, Hatakeyama S, Narita S, Habuchi T, Mori K, Koie T, Ohyama C
  • Organizer: 第29回欧州泌尿器科学会（EAU）
  • Place of Presentation: ストックホルム
  • Year and Date: 2014-04-11 – 2014-04-15
• [Presentation] Laminin binding glycan depletion on α-dystroglycan in prostate cancer cells promotes epithelial-mesenchymal transition and enhances tumor formation. (2014)
  • Author(s): Yoneyama T, Hatakeyama S, Tobisawa Y, Koie T, Ohyama C, Fukuda M
  • Organizer: 第29回欧州泌尿器科学会（EAU）
  • Place of Presentation: ストックホルム
  • Year and Date: 2014-04-11 – 2014-04-15
• [Presentation] Glycan modification of podoplanin enhances growth factor production through stabilization of platelet aggregation in bladder cancer cell. (2014)
  • Author(s): Tobisawa Y, Yoneyama T, Hatakeyama S, Yamamoto H, Okamoto T, Imai A, Yoneyama T, Hashimoto Y, Koie T, Ohyama C
  • Organizer: 第29回欧州泌尿器科学会（EAU）
  • Place of Presentation: ストックホルム
  • Year and Date: 2014-04-11 – 2014-04-15
• [Presentation] Immunohistochemical detection of core2 β-1, 6-N-acetylglucosaminyltransferase is an independent risk factor for PSA recurrence after radical prostatectomy. (2014)
  • Author(s): Tobisawa Y, Yoneyama T, Hatakeyama S, Yamamoto H, Okamoto T, Imai A, Yoneyama T, Hashimoto Y, Koie T, Ohyama C
  • Organizer: 第29回欧州泌尿器科学会（EAU）
  • Place of Presentation: ストックホルム
  • Year and Date: 2014-04-11 – 2014-04-15
• [Presentation] Glycan modification of surface glycoproteins on prostate cancer induces secretion of growth factors via enhanced interaction with prostate stromal cells. (2014)
  • Author(s): Tobisawa Y, Hatakeyama S, Yoneyama T, Okamoto T, Yamamoto H, Imai A, Yoneyama T, Hashimoto Y, Koie T, Ohyama C
  • Organizer: 第29回欧州泌尿器科学会（EAU）
  • Place of Presentation: ストックホルム
  • Year and Date: 2014-04-11 – 2014-04-15
• [Presentation] Immunohistochemical detection of core2 β-1, 6-N- acetylglucosaminyltransferase is an independent risk factor for PSA recurrence after radical prostatectomy. (2014)
  • Author(s): Ohyama C
  • Organizer: East Asia Urological Cancer Symposium
  • Place of Presentation: Seoul, Korea
  • Invited
• [Presentation] Immunohistochemical detection of core2 β-1, 6-N- acetylglucosaminyltransferase is an independent risk factor for PSA recurrence after radical prostatectomy. (2013)
  • Author(s): Tobisawa Y, Yoneyama T, Hatakeyama S, Yamamoto H, Sugiyama N, Suzuki Y, Okamoto A, Okamoto T, Imai A, Yoneyama T, Hashimoto Y, Oikawa M, Narita T, Hagiwara K, Koie T, Ohyama C
  • Organizer: 米国泌尿器科学会年次総会（AUA 2013）
  • Place of Presentation: San Diego, CA, USA
• [Patent(Industrial Property Rights)] 抗コア２β1,6NアセチルグルコサミニルトランスフェラーゼＩモノクローナル抗体を利用して癌の悪性度を診断する方法 (2012)
  • Inventor(s): 大山 力
  • Industrial Property Rights Holder: 大山 力
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2012-232564
  • Filing Date: 2012-10-22