Development of kidney cancer biomarker for therapeutic efficacy by using imaging and liquid biopsy

• Project/Area Number: 18K16719
• 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: Hosogoe Shogo 弘前大学, 医学研究科, 客員研究員 (00815798)
• 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: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 腎細胞癌 / 糖鎖解析 / 腎癌 / バイオマーカー / 糖鎖 / Liquid biopsy / リキッドバイオプシー / 治療効果判定 / 画像診断法

Outline of Final Research Achievements

Advanced/metastatic renal cell carcinoma (RCC) is a disease with a poor prognosis without useful biomarkers. In this study, we aimed to establish a liquid biopsy-based biomarkers using comprehensive glycosylation of serum and cell free DNA (cfDNA). We analyzed 100 samples to select the candidate molecules (glycans and genes). We developed diagnostic N-glycan score to detect RCC. We found diagnostic N-glycan score were useful to detect RCC with a high accuracy. We found the G250 gene, which is specific for RCC, was not useful. Further study is necessary to examine whether biomarkers using glycans correlate with images in the future.

Academic Significance and Societal Importance of the Research Achievements

本研究は、有効なバイオマーカーがない腎細胞癌において、血清糖鎖測定が診断に有効であることを示した研究である。一般に糖鎖解析には専門的な知識だけでなく質量分析装置が必要になるため、実臨床での多数検体を測定することはかなり困難であった。しかし本研究では、糖鎖解析にキャピラリー電気泳動法を応用することで、扱いが煩雑な質量分析装置を用いずとも糖鎖解析が可能であり、更にそのスコア化により、疾患の診断が可能であることを示唆することができた。cfDNAや循環腫瘍細胞、画像評価との相関はこれからであるが、本研究の研究成果の学術的意義や社会的意義は大きいものと思われる。

Research Products

• [Journal Article] Trends in the use of neoadjuvant chemotherapy and oncological outcomes for high‐risk upper tract urothelial carcinoma: a multicentre retrospective study (2021)
  • Author(s): Hamaya Tomoko、Hatakeyama Shingo、Tanaka Toshikazu、Kubota Yuka、Togashi Kyo、Hosogoe Shogo、Fujita Naoki、Kusaka Ayumu、Tokui Noriko、Okamoto Teppei、Yamamoto Hayato、Yoneyama Tohru、Yoneyama Takahiro、Hashimoto Yasuhiro、Ohyama Chikara
  • Journal Title: BJU International Volume: - Issue: 4 Pages: 468-476
  • DOI: 10.1111/bju.15346
  • Peer Reviewed / Open Access
• [Journal Article] Comparison of nivolumab plus ipilimumab with tyrosine kinase inhibitors as first-line therapies for metastatic renal-cell carcinoma: a multicenter retrospective study (2020)
  • Author(s): Kido Koichi、Hatakeyama Shingo、Numakura Kazuyuki、Tanaka Toshikazu、Oikawa Masaaki、Noro Daisuke、Hosogoe Shogo、Narita Shintaro、Inoue Takamitsu、Yoneyama Takahiro、Ito Hiroyuki、Nishimura Shoji、Hashimoto Yasuhiro、Kawaguchi Toshiaki、Habuchi Tomonori、Ohyama Chikara
  • Journal Title: International Journal of Clinical Oncology Volume: 26 Issue: 1 Pages: 154-162
  • DOI: 10.1007/s10147-020-01797-5
  • Peer Reviewed / Open Access
• [Journal Article] Efficacy and safety of first‐line nivolumab plus ipilimumab in patients with metastatic renal cell carcinoma: A multicenter retrospective study (2020)
  • Author(s): Tanaka Toshikazu、Hatakeyama Shingo、Numakura Kazuyuki、Kido Koichi、Noro Daisuke、Oikawa Masaaki、Hosogoe Shogo、Tokui Noriko、Yamamoto Hayato、Narita Shintaro、Ito Hiroyuki、Yoneyama Takahiro、Hashimoto Yasuhiro、Kawaguchi Toshiaki、Habuchi Tomonori、Ohyama Chikara
  • Journal Title: International Journal of Urology Volume: 27 Issue: 12 Pages: 1095-1100
  • DOI: 10.1111/iju.14363
  • Peer Reviewed
• [Journal Article] Proton pump inhibitor as an independent factor of progression of abdominal aortic calcification in patients on maintenance hemodialysis (2018)
  • Author(s): Okamoto Teppei、Hatakeyama Shingo、Hosogoe Shogo、Tanaka Yoshimi、Imanishi Kengo、Takashima Toru、Saitoh Fumitada、Suzuki Tadashi、Ohyama Chikara
  • Journal Title: PLOS ONE Volume: 13 Issue: 7 Pages: 199160-199160
  • DOI: 10.1371/journal.pone.0199160
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The relationship between poor nutritional status and progression of aortic calcification in patients on maintenance hemodialysis (2018)
  • Author(s): Okamoto Teppei、Hatakeyama Shingo、Kodama Hirotake、Horiguchi Hirotaka、Kubota Yuka、Kido Koichi、Momota Masaki、Hosogoe Shogo、Tanaka Yoshimi、Takashima Tooru、Saitoh Fumitada、Suzuki Tadashi、Ohyama Chikara
  • Journal Title: BMC Nephrology Volume: 19 Issue: 1 Pages: 0001-0001
  • DOI: 10.1186/s12882-018-0872-y
  • Peer Reviewed / Open Access / Int'l Joint Research