Biomarker screening of urothelial carcinoma using liquid biopsy

• Project/Area Number: 19K18575
• 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: Suzuki Yuichiro 弘前大学, 医学研究科, 客員研究員 (50647344)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 尿路上皮癌 / 糖鎖解析 / Urothelial carcinoma / Biomarker / Glycan / cell free DNA

Outline of Research at the Start

Liquid biopsyによる網羅的解血清糖鎖析、CTC細胞表面糖鎖、糖転移酵素の発現定量およびcfDNA中の糖転移酵素の発現検出法の確立と、それを用いた尿路上皮癌の悪性度・再発・効果予測への有用性を明らかとする.
尿路上皮癌と診断され治療予定の患者の治療前後検体、もしくは転移性尿路上皮癌患者の定期採血検体からCTCおよびcfDNAを分離し、糖鎖抗原・糖転移酵素の発現量やcfDNA中の糖転移酵素コピー数をモニタリングし、病理学的悪性度、抗癌剤・免疫チェックポイント阻害剤による治療効果、治療抵抗性獲得や予後との関連を検討する。

Outline of Final Research Achievements

Locally advanced or metastatic urothelial carcinoma has a poor prognosis. Early detection is important, but accurate diagnosis requires invasive tests such as cystoscopy and ureteroscopy, and minimally invasive and effective biomarkers have not been developed. We analyzed serum glycan profiling of urothelial carcinoma patients using a comprehensive glycan profiling system. The results suggested changes in immunoglobulin-associated glycans. The glycan structures of immunoglobulins were examined, suggesting that characteristic glycans may be altered, and machine learning analysis suggested high diagnostic accuracy. Prognosis prediction by combining glycan analysis and cell-free DNA is a subject for future study.

Academic Significance and Societal Importance of the Research Achievements

局所進行性もしくは転移性の尿路上皮癌は予後不良の疾患である。早期発見が重要であるが、正確な診断には膀胱鏡・尿管鏡などの侵襲的な検査が必要であり、低侵襲かつ有効なバイオマーカーは開発されていない。本研究は、有効なバイオマーカーのない尿路上皮癌に焦点を当て、免疫グロブリンの糖鎖変化が診断マーカーになりうる可能性を示した。免疫グロブリンの糖鎖構造を検討したところ、特徴的な糖鎖が変化している可能性が示唆され、機械学習を用いた解析から、高い診断精度が示唆された。機器の普及など課題はあるが、本研究成果の学術的意義や社会的意義は非常に大きいと思われる。

Research Products

• [Journal Article] The effect of number of treatment cycles of platinum-based first-line chemotherapy on maximum radiological response in patients with advanced urothelial carcinoma (2021)
  • Author(s): Okita Kazutaka、Hatakeyama Shingo、Hagiwara Kazuhisa、Suzuki Yuichiro、Tanaka Toshikazu、Noro Daisuke、Tokui Noriko、Fujita Naoki、Konishi Sakae、Okamoto Teppei、Yoneyama Tohru、Yamamoto Hayato、Yoneyama Takahiro、Hashimoto Yasuhiro、Ohyama Chikara
  • Journal Title: Urologic Oncology: Seminars and Original Investigations Volume: - Issue: 12 Pages: 832.e17-832.e23
  • DOI: 10.1016/j.urolonc.2021.03.011
  • Peer Reviewed
• [Journal Article] Living Kidney Transplantation From Marginal Donors Presents Feasible Donor Renal Function Despite Inferior Recipient Renal Function (2020)
  • Author(s): Hamano Itsuto、Hatakeyama Shingo、Fujita Takeshi、Murakami Reiichi、Hamaya Tomoko、Togashi Kyo、Suzuki Yuichiro、Yamamoto Hayato、Yoneyama Tohru、Yoneyama Takahiro、Hashimoto Yasuhiro、Narumi Shunji、Tomita Hirofumi、Ohyama Chikara
  • Journal Title: Transplantation Proceedings Volume: 52 Issue: 6 Pages: 1723-1728
  • DOI: 10.1016/j.transproceed.2020.01.157
  • Peer Reviewed
• [Journal Article] Outcome of ABO Blood Type Incompatible Living-Related Donor Kidney Transplantation Under a Contemporary Immunosuppression Strategy in Japan (2020)
  • Author(s): Hamano Itsuto、Hatakeyama Shingo、Fujita Takeshi、Murakami Reiichi、Hamaya Tomoko、Togashi Kyo、Suzuki Yuichiro、Yamamoto Hayato、Yoneyama Tohru、Yoneyama Takahiro、Hashimoto Yasuhiro、Narumi Shunji、Tomita Hirofumi、Ohyama Chikara
  • Journal Title: Transplantation Proceedings Volume: 52 Issue: 6 Pages: 1700-1704
  • DOI: 10.1016/j.transproceed.2020.01.152
  • Peer Reviewed
• [Journal Article] Serum N-glycan profiling can predict biopsy-proven graft rejection after living kidney transplantation. (2020)
  • Author(s): Soma O, Hatakeyama S, Yoneyama T, Saito M, Sasaki H, Tobisawa Y, Noro D, Suzuki Y, Tanaka M, Nishimura SI, Harada H, Ishida H, Tanabe K, Satoh S, Ohyama C.
  • Journal Title: Clin Exp Nephrol Volume: 24 Issue: 2 Pages: 174-184
  • DOI: 10.1007/s10157-019-01820-8
  • Peer Reviewed
• [Journal Article] Influence of pretreatment quality of life on prognosis in patients with urothelial carcinoma. (2020)
  • Author(s): Suppanuntaroek S, Hatakeyama S, Fujita N, Kubota Y, Suzuki Y, Okamoto T, Tobisawa Y, Yoneyama T, Yamamoto H, Mori K, Imai A, Yoneyama T, Hashimoto Y, Ohyama C.
  • Journal Title: Int J Clin Oncol. Volume: 25 Issue: 2 Pages: 362-369
  • DOI: 10.1007/s10147-019-01563-2
  • Peer Reviewed / Int'l Joint Research