Identification of renal cancer biomarkers using comprehensive glycan analysis

• Project/Area Number: 20K18083
• 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: Kodama Hirotake 弘前大学, 医学研究科, 客員研究員 (50817294)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2022: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 糖鎖 / 腎癌 / 糖鎖解析 / キャピラリー電気泳動装置

Outline of Research at the Start

腎癌の診断、再発の評価は画像診断を中心に行われているが、有効な腫瘍マーカーが存在しないため、進行癌で診断されるケースも30％程度とされている。さらに正確な診断には腎生検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。弘前大学泌尿器科では血清N型糖鎖構造の網羅的質量解析により、画像診断とともに腎癌の早期診断補助となるバイオマーカーとして有用な糖鎖変異を同定したが、臨床応用には質量分析法が大きなハードルであった。本研究では、N-結合型糖鎖を短時間で、網羅的に解析可能なキャピラリー電気泳動装置（GlyQ）による糖鎖解析を用いて腎癌の新規診断マーカーの臨床応用を目指す。

Outline of Final Research Achievements

Since there are no tumor markers for renal cancer, there is a need for effective biomarker development. In this study, we developed a novel diagnostic marker for renal cancer using glycan analysis by capillary electrophoresis system (GlyQ), which can analyze N-linked sugar chains in a short time and comprehensively. We developed a new diagnostic biomarker for renal cancer diagnosis using GlyQ with machine learning, suggesting that it can discriminate renal cancer with high accuracy. However, it was also found that GlyQ is not useful for predicting the prognosis of renal cancer. These results suggest that glycosylated renal cancer biomarkers may be effective in the diagnosis of renal cancer.

Academic Significance and Societal Importance of the Research Achievements

画像診断技術の進歩によって腎癌の発見頻度は増加してきているが、早期診断マーカーがないため、約30%は進行性・転移性である。また再発マーカーもなく、再発して画像で見えるまでは診断法がないことから、低侵襲な腎癌診断マーカーの実用化が求められている。本研究では、糖鎖性バイオマーカーを用いて、高精度に腎癌を判別できることが示唆された。しかし腎癌の予後予測には限界があることも判明し、更なる検討が必要であることが示された。まだまだ検討は必要であるが、糖鎖性バイオマーカーの有効性を示した本研究の成果の学術的意義や社会的意義は大きいと思われる。

Research Products

• [Journal Article] Kidney Transplantation in a Patient With Noonan Syndrome: A Case Report (2022)
  • Author(s): Kodama Hirotake; Hatakeyama Shingo; Hamaya Tomoko; Murakami Reiichi; Murasawa Hiromi; Yamamoto Hayato; Yoneyama Takahiro; Ohyama Chikara
  • Journal Title: Transplant Proc Volume: 54 Issue: 6 Pages: 1601-1603
  • DOI: 10.1016/j.transproceed.2022.03.051
  • Peer Reviewed
• [Journal Article] Significance of pelvic lymph node dissection during radical prostatectomy in high-risk prostate cancer patients receiving neoadjuvant chemohormonal therapy (2022)
  • Author(s): Hiromichi Iwamura, Shingo Hatakeyama, Takuma Narita, Yusuke Ozaki, Sakae Konishi, Hirotaka Horiguchi, Hirotake Kodama, Yuta Kojima, Naoki Fujita, Teppei Okamoto, Yuki Tobisawa, Tohru Yoneyama, Hayato Yamamoto, Takahiro Yoneyama, Yasuhiro Hashimoto, Chikara Ohyama
  • Journal Title: Scientific reports Volume: 12 Issue: 1 Pages: 9675-9675
  • DOI: 10.1038/s41598-022-13651-x
  • Peer Reviewed / Open Access
• [Journal Article] Machine learning diagnosis by immunoglobulin N-glycan signatures for precision diagnosis of urological diseases (2022)
  • Author(s): Iwamura H, Mizuno K, Akamatsu S, Hatakeyama S, Tobisawa Y, Narita S, Narita T, Yamashita S, Kawamura S, Sakurai T, Fujita N, Kodama H, Noro D, Kakizaki I, Nakaji S, Itoh K, Tsuchiya N, Ito A, Habuchi T, Ohyama C, Yoneyama T
  • Journal Title: Cancer Science Volume: 113 Issue: 7 Pages: 2434-2445
  • DOI: 10.1111/cas.15395
  • Peer Reviewed / Open Access
• [Journal Article] Seroprevalence of SARS-CoV-2 spike IgG antibodies after the second BNT162b2 mRNA vaccine in Japanese kidney transplant recipients (2022)
  • Author(s): Hamaya Tomoko; Hatakeyama Shingo; Yoneyama Tohru; Tobisawa Yuki; Kodama Hirotake; Fujita Takeshi; Murakami Reiichi; Fujita Naoki; Okamoto Teppei; Yamamoto Hayato; Yoneyama Takahiro; Hashimoto Yasuhiro; Saitoh Hisao; Narumi Shunji; Tomita Hirofumi; Ohyama Chikara
  • Journal Title: Sci Rep Volume: 12(1) Issue: 1 Pages: 5876-5876
  • DOI: 10.1038/s41598-022-09897-0
  • Peer Reviewed / Open Access
• [Journal Article] Characteristics of α2,3‐sialyl N‐glycosylated PSA as a biomarker for clinically significant prostate cancer in men with elevated PSA level (2021)
  • Author(s): Yoneyama Tohru、Yamamoto Hayato、Sutoh Yoneyama Mihoko、Tobisawa Yuki, Hatakeyama Shingo, Narita Takuma, Ohyama Chikara, et al.
  • Journal Title: The Prostate Volume: 81 Issue: 16 Pages: 1411-1427
  • DOI: 10.1002/pros.24239
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] N‐glycan signature of serum immunoglobulins as a diagnostic biomarker of urothelial carcinomas (2021)
  • Author(s): Kodama Hirotake、Yoneyama Tohru、Tanaka Toshikazu、Noro Daisuke、Tobisawa Yuki、Yamamoto Hayato、Suto Shinichiro、Hatakeyama Shingo、Mori Kazuyuki、Yoneyama Takahiro、Hashimoto Yasuhiro、Kakizaki Ikuko、Nakaji Shigeyuki、Ohyama Chikara
  • Journal Title: Cancer Medicine Volume: 10 Issue: 4 Pages: 1297-1313
  • DOI: 10.1002/cam4.3727
  • Peer Reviewed
• [Journal Article] Effect of frailty and comorbidity on surgical contraindication in patients with localized prostate cancer (FRART-PC Study) (2021)
  • Author(s): Kodama Hirotake、Hatakeyama Shingo、Momota Masaki、Togashi Kyo、Hamaya Tomoko、Hamano Itsuto、Fujita Naoki、Kojima Yuta、Okamoto Teppei、Yoneyama Tohru、Yamamoto Hayato、Yoshikawa Kazuaki、Yoneyama Takahiro、Hashimoto Yasuhiro、Ohyama Chikara
  • Journal Title: Urologic Oncology: Seminars and Original Investigations Volume: 39 Issue: 3 Pages: 191.e1-191.e8
  • DOI: 10.1016/j.urolonc.2020.06.019
  • Peer Reviewed / Open Access