establishment of early diagnostic method in gastric cancer using exosome RNA

• Project/Area Number: 17K10583
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Mie University
• Principal Investigator: Yoshiyama Shigeyuki 三重大学, 医学系研究科, リサーチアソシエイト (60444436)
• Co-Investigator(Kenkyū-buntansha): 問山 裕二 三重大学, 医学系研究科, 准教授 (00422824) ; 楠 正人 三重大学, 医学系研究科, 名誉教授 (50192026) ; 安田 裕美 三重大学, 医学部附属病院, 学内講師 (60586767) ; 毛利 靖彦 三重大学, 医学系研究科, リサーチアソシエイト (70345974)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2017: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 胃癌 / バイオマーカー / エキソソーム / エクソソーム / 外科

Outline of Final Research Achievements

We extracted exosomal-RNA from the culture-supernatant of gastric cancer cell line and gastric stromal cell line by the method mentioned separately, offered microRNA-array to outsource, then analyzed the data and identified 12 miRNAs which were significantly dysregulated in gastric cancer cell line. As a preliminay study, exosomal RNA was extracted from the sera of gastric cancer patients (n = 10) and healthy subjects (n = 10). Then the candidate miRNAs were quantified by qRT-PCR method, and risk score was created by statistical software. The risk score was significantly higher in gastric cancer patients than that in healthy controls (P <0.0001), and discriminated gastric cancer patients by the accuracy of Area Under Curve (AUC): 0.966.

Academic Significance and Societal Importance of the Research Achievements

細胞から分泌される細胞外微小小胞であるエクソソームは、癌細胞からも血液中に分泌され、癌細胞から分泌されたエクソソームは目的の細胞へと運ばれ，細胞間や組織へのシグナル伝達をおこない、癌進展や転移に関与する事が明らかになってきている。エクソソーム内に包埋されたmicroRNAsはヒト生体内で安定した状態で存在し、癌種ごとに特異的プロファイリングを形成するとされ、胃癌においても新規のバイオマーカー分野として深く探求していくに値するものと考えられる。

Research Products

• [Journal Article] Genomewide Expression Profiling Identifies a Novel miRNA-Based Signature for the Detection of Peritoneal Metastasis in Patients With Gastric Cancer (2019)
  • Author(s): Shimura Tadanobu、Toden Shusuke、Kandimalla Raju、Toiyama Yuji、Okugawa Yoshinaga、Kanda Mitsuro、Baba Hideo、Kodera Yasuhiro、Kusunoki Masato、Goel Ajay
  • Journal Title: Annals of Surgery Volume: - Issue: 5 Pages: 1-1
  • DOI: 10.1097/sla.0000000000003647
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Soluble PD-L1 Expression in Circulation as a Predictive Marker for Recurrence and Prognosis in Gastric Cancer: Direct Comparison of the Clinical Burden Between Tissue and Serum PD-L1 Expression. (2019)
  • Author(s): Shigemori T, Toiyama Y, Okugawa Y, Yamamoto A, Yin C, Narumi A, Ichikawa T, Ide S, Shimura T, Fujikawa H, Yasuda H, Hiro J, Yoshiyama S, Ohi M, Araki T, Kusunoki M.
  • Journal Title: Ann Surg Oncol. Volume: 26 Issue: 3 Pages: 876-883
  • DOI: 10.1245/s10434-018-07112-x
  • Peer Reviewed / Open Access
• [Presentation] 胃癌腹膜播種に特異的なmicroRNAパネルの同定ならびにその臨床的意義 (2019)
  • Author(s): 志村匡信、問山裕二、奥川喜永、東田周祐、安田裕美、吉山繁幸、大井正貴、荒木俊光、楠 正人、Ajay Goel
  • Organizer: 第74回日本消化器外科学会総会