Development of GCNT2 glycosyltransferase-based liquid biopsy marker for evaluation of prostate cancer malignancy

• Project/Area Number: 18K16717
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56030:Urology-related
• Research Institution: Hirosaki University
• Principal Investigator: Mikami Jotaro 弘前大学, 医学研究科, 客員研究員 (10792319)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: リキッドバイオプシー / 前立腺癌 / 糖転移酵素 / GCNT2

Outline of Final Research Achievements

In this study, we evaluate the glycosyltransferase gene expression in cell free DNA as a biomarker of prostate cancer malignancy or as a surrogate biomarker of treatment of prostate cancer. The expression level of LacdiNAc-glycan synthesis related B4GALNT4 gene significantly correlate with castration resistant status of prostate cancer suggesting the B4GALNT4 gene expression in cfDNA as a prognostic biomarker of castration resistant prostate cancer. The expression level of I antigen-glycan synthesis related GCNT2 gene was not significant correlation in prostate cancer detection and evaluation of its malignancy.

Academic Significance and Societal Importance of the Research Achievements

本研究では前立癌診断や悪性度評価に関わるマーカーを同定するには至らなかったが、cfDNA中の糖転移酵素の発現定量による去勢抵抗性前立腺癌の予後予測に関連する遺伝子を同定した。特に骨転移が多く、針生検による、組織検体採取が難しい去勢抵抗性前立腺癌の予後予測および治療効果モニタリングには、低侵襲なLiquid biopsyベースのバイオマーカーが非常に有用であると考えられる。cfDNA中の糖転移酵素バイオマーカーは、これまでに報告されておらず、学術的意義は高く、本バイオマーカーの実用化は、去勢抵抗性前立腺癌の治療効果の向上、患者のQOL向上および医療費軽減につながり、社会的意義は大きい。

Research Products

• [Journal Article] Preoperative pelvic floor muscle exercise for early continence after holmium laser enucleation of the prostate: a randomized controlled study (2020)
  • Author(s): Anan Go、Kaiho Yasuhiro、Iwamura Hiromichi、Ito Jun、Kohada Yuki、Mikami Jotaro、Sato Makoto
  • Journal Title: BMC Urology Volume: 20 Issue: 1 Pages: 3-3
  • DOI: 10.1186/s12894-019-0570-5
• [Journal Article] The Impact of Glycosylation of Osteopontin on Urinary Stone Formation (2019)
  • Author(s): Anan Go、Yoneyama Tohru、Noro Daisuke、Tobisawa Yuki、Hatakeyama Shingo、Sutoh Yoneyama Mihoko、Yamamoto Hayato、Imai Atsushi、Iwamura Hiromichi、Kohada Yuki、Mikami Jotaro、Ito Jun、Kaiho Yasuhiro、Yoneyama Takahiro、Hashimoto Yasuhiro、Sato Makoto、Ohyama Chikara
  • Journal Title: International Journal of Molecular Sciences Volume: 21 Issue: 1 Pages: 93-93
  • DOI: 10.3390/ijms21010093
  • Peer Reviewed / Open Access