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Development of a new companion diagnostic for immune CP inhibitors for metastatic urothelial cancer using glycan analysis

Research Project

Project/Area Number 21K09364
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56030:Urology-related
Research InstitutionHirosaki University

Principal Investigator

Hashimoto Yasuhiro  弘前大学, 医学研究科, 准教授 (60322939)

Co-Investigator(Kenkyū-buntansha) 山本 勇人  弘前大学, 医学研究科, 准教授 (30532759)
米山 高弘  弘前大学, 医学部付属病院, 准教授 (90374834)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2023: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2022: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2021: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Keywords糖鎖解析 / 尿路上皮癌 / 免疫CP阻害剤 / 転移性尿路上皮癌 / コンパニオン診断
Outline of Research at the Start

免疫チェックポイント(CP)阻害剤が開発され、日本でも再発または転移性尿路上皮癌に対してペンブロリズマブが承認され予後の向上が期待されている。実際使用すると劇的に転移巣が縮小する症例もみられるが、効果不十分の症例も多くみられるのが現状である。
本研究では、血清N-結合型糖鎖の網羅的質量解析によって転移性尿路上皮患者の免疫CP阻害剤の治療効果を予測する新規診断マーカーの開発を目標とする。

Outline of Final Research Achievements

In recent years, there has been an increase in the use of immune checkpoint inhibitors for patients with metastatic urothelial carcinoma due to their inclusion in insurance coverage. While some cases have shown dramatic effectiveness, more than half exhibit insufficient response, underscoring the need for biomarkers to predict efficacy before treatment initiation. We have contemplated the development of biomarkers for predicting the efficacy of immune checkpoint inhibitors through comprehensive mass analysis of serum N-linked glycans.
Using the Gly-Q capillary electrophoresis system and machine learning with DataRobot, we identified two types of glycans from the 26 N-glycan structures in serum immunoglobulin fractions as potential candidates for assessing treatment efficacy. We plan to further investigate by increasing the number of cases in the future

Academic Significance and Societal Importance of the Research Achievements

転移性の尿路上皮癌は予後不良の疾患である。免疫CP阻害剤はその転移性尿路上皮癌に使用されるが、非常に効果のある症例もある反面、半数以上は効果不十分である。今回の我々の検討では特徴的な糖鎖の変化と免疫CP阻害剤の治療効果が相関する可能性があることが示された。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。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (7 results)

All 2023 2022 2021

All Journal Article (7 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 7 results,  Open Access: 7 results)

  • [Journal Article] Impact of an optimized surveillance protocol based on the European Association of Urology substratification on surveillance costs in patients with primary high-risk non-muscle-invasive bladder cancer2023

    • Author(s)
      Fujita Naoki、Hatakeyama Shingo、Okita Kazutaka、Momota Masaki、Tobisawa Yuki、Yoneyama Tohru、Yamamoto Hayato、Ito Hiroyuki、Yoneyama Takahiro、Hashimoto Yasuhiro、Yoshikawa Kazuaki、Ohyama Chikara
    • Journal Title

      PLOS ONE

      Volume: 18 Issue: 2 Pages: 0275921-0275921

    • DOI

      10.1371/journal.pone.0275921

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Combination of Muscle Quantity and Quality Is Useful to Assess the Necessity of Surveillance after a 5-Year Cancer-Free Period in Patients Who Undergo Radical Cystectomy: A Multi-Institutional Retrospective Study.2023

    • Author(s)
      Fujita N, Momota M, Horiguchi H, Hamano I, Mikami J, Hatakeyama S, Ito H, Yoneyama T, Hashimoto Y, Nishimura S, Yoshikawa K, Ohyama C.
    • Journal Title

      Cancers (Basel)

      Volume: 15(5) Issue: 5 Pages: 1489-1489

    • DOI

      10.3390/cancers15051489

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Impact of nephroureterectomy on postoperative renal function in upper tract urothelial carcinoma: A multicenter retrospective study2023

    • Author(s)
      Okuyama Yoshiharu、Hatakeyama Shingo、Tabata Ryuji、Fujimori Daiji、Kawashima Yohei、Tanaka Toshikazu、Fujita Naoki、Okamoto Teppei、Mori Kazuyuki、Yamamoto Hayato、Yoneyama Takahiro、Hashimoto Yasuhiro、Matsuoka Toshimitsu、Sato Satoshi、Ohyama Chikara
    • Journal Title

      International Journal of Urology

      Volume: 30 Issue: 8 Pages: 649-657

    • DOI

      10.1111/iju.15192

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Oncological and functional outcomes of female reproductive organ-sparing radical cystectomy and ileal neobladder construction2022

    • Author(s)
      Miura Hikari、Hatakeyama Shingo、Tanaka Toshikazu、Fujita Naoki、Horiguchi Hirotaka、Tanaka Ryuma、Noro Daisuke、Tokui Noriko、Okamoto Teppei、Yamamoto Hayato、Yoneyama Takahiro、Hashimoto Yasuhiro、Ohyama Chikara
    • Journal Title

      Urologic Oncology: Seminars and Original Investigations

      Volume: - Issue: 5 Pages: 254.e17-254.e24

    • DOI

      10.1016/j.urolonc.2022.11.018

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] TMEM2 expression is downregulated as bladder cancer invades the muscle layer2022

    • Author(s)
      Yoneyama Mihoko Sutoh、Yoneyama Tohru、Tobisawa Yuki、Yamamoto Hayato、Hatakeyama Shingo、Yoneyama Takahiro、Hashimoto Yasuhiro、Suzuki Tadashi、Ohyama Chikara
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 613 Pages: 1-6

    • DOI

      10.1016/j.bbrc.2022.04.118

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Association of oncological response between the first‐line chemotherapy and subsequent immune checkpoint inhibitors therapy in patients with unresectable or metastatic urothelial carcinoma2021

    • Author(s)
      Ozaki Kai、Hatakeyama Shingo、Hamaya Tomoko、Okita Kazutaka、Hashimoto Yasuhiro、Ohyama Chikara
    • Journal Title

      International Journal of Urology

      Volume: 29 Issue: 4 Pages: 362-364

    • DOI

      10.1111/iju.14778

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Comparison of pembrolizumab with conventional chemotherapy after first‐line platinum‐based chemotherapy for advanced urothelial carcinoma in real‐world practice: A multicenter retrospective study2021

    • Author(s)
      Narita Takuma、Hatakeyama Shingo、Numakura Kazuyuki、Kobayashi Mizuki、Muto Yumina、Saito Mitsuru、Narita Shintaro、Tanaka Toshikazu、Noro Daisuke、Tokui Noriko、Yoneyama Takahiro、Hashimoto Yasuhiro、Habuchi Tomonori、Ohyama Chikara
    • Journal Title

      International Journal of Urology

      Volume: 28 Issue: 9 Pages: 899-905

    • DOI

      10.1111/iju.14601

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research

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Published: 2021-04-28   Modified: 2025-01-30  

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