Development of a circulating miRNA-based diagnostic signature forearly detection of gastric cancer

• Project/Area Number: 18K16261
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55010:General surgery and pediatric surgery-related
• Research Institution: Kumamoto University
• Principal Investigator: Yamamura Kensuke 熊本大学, 病院, 特任助教 (10816507)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 胃癌 / マイクロRNA / signature / バイオマーカー / micro RNA

Outline of Final Research Achievements

Currently endoscopic surveillance is the gold standard for gastric cancer (GC) diagnosis, but remains as an ineffective screening strategy due to its invasiveness and associated costs. Herein, by integrating high-throughput data analysis, followed by comprehensive tissue and serum validations, we aimed to establish a circulating miRNA-based diagnostic signature for early detection of GC. We have developed a robust diagnostic marker for GC through integration of comprehensive high-throughput data analysis as well as clinical validation involving over 1200 GC samples across 6 independent cohorts. Collectively, our data demonstrates clinical significance of circulating-miRNA-signature for early detection of GC.

Academic Significance and Societal Importance of the Research Achievements

現在胃癌の診断はコストが高く侵襲を伴っている。安価で非侵襲的なバイオマーカーの探索は以前からなされているが、確立されたものは少なくいわば古くて新しい課題である。本研究では、オンラインで入手可能な複数の胃癌組織の網羅的解析データファイル及びグローバルに集められた600例以上の臨床サンプルを用いて、より精度が高く侵襲の少ない胃癌診断のためのマイクロRNA signatureを開発した。本研究で得られた結果は、末梢血から早期胃癌を診断可能なバイオマーカーの開発につながる可能性がある。

Research Products

• [Journal Article] A 15-gene immune, stromal and proliferation gene signature that significantly associates with poor survival in patients with pancreatic ductal adenocarcinoma (2020)
  • Author(s): Kandimalla Raju、Tomihara Hideo、Banwait Jasjit K、Yamamura Kensuke、Singh Gagandeep、Baba Hideo、Goel Ajay
  • Journal Title: Clinical Cancer Research Volume: 26 Issue: 14 Pages: 3641-3648
  • DOI: 10.1158/1078-0432.ccr-19-4044
  • Peer Reviewed
• [Journal Article] Intratumoral Fusobacterium Nucleatum Levels Predict Therapeutic Response to Neoadjuvant Chemotherapy in Esophageal Squamous Cell Carcinoma (2019)
  • Author(s): Yamamura Kensuke、Izumi Daisuke、Kandimalla Raju、Sonohara Fuminori、Baba Yoshifumi、Yoshida Naoya、Kodera Yasuhiro、Baba Hideo、Goel Ajay
  • Journal Title: Clinical Cancer Research Volume: 25 Issue: 20 Pages: 6170-6179
  • DOI: 10.1158/1078-0432.ccr-19-0318
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Controlling Nutritional Status (CONUT) score is a prognostic marker for gastric cancer patients after curative resection. Gastric Cancer. (2018)
  • Author(s): Kuroda D, Sawayama H, Kurashige J, Iwatsuki M, Eto T, Tokunaga R, Kitano Y, Yamamura K, Ouchi M, Nakamura K, Baba Y, Sakamoto Y, Yamashita Y, Yoshida N, Chikamoto A, Baba H
  • Journal Title: Gastric Cancer. Volume: 21(2) Issue: 2 Pages: 204-212
  • DOI: 10.1007/s10120-017-0744-3
  • Peer Reviewed
• [Presentation] Identification and establishment of a novel, circulating miRNA signature, for pre-operative diagnosis of occult distant metastasis in patients with pancreatic ductal adenocarcinoma (2019)
  • Author(s): 1.Kensuke Yamamura, Susan Tsai, Jasjit Kaur Banwait, Fuminori Sonohara, Yo-ichi Yamashita, Douglas B Evans, Yasuhiro Kodera, Hideo Baba, and Ajay Goel
  • Organizer: AACR 2019
  • Int'l Joint Research
• [Presentation] Genomewide expression profiling identifies a novel gene-expression signature for recurrence prediction in patients with early-onset colorectal cancer (EOCRC) (2019)
  • Author(s): 2.Kensuke Yamamura, Lina Zhu, Raju Kandimalla, Daisuke Izumi, Takatoshi Matsuyama, Yusuke Kinugasa, Francesc Balaguer, Hideo Baba, Xin Wang and Ajay Goel
  • Organizer: AACR 2019
  • Int'l Joint Research