Achievement of highly accurate diagnosis of early pancreatic cancer in Japanese patients through a comprehensive/integrated approach

• Project/Area Number: 15H05791
• Research Category: Grant-in-Aid for Scientific Research (S)
• Allocation Type: Single-year Grants
• Research Field: Digestive surgery
• Research Institution: Kyushu University (2018-2019); Osaka University (2015-2017)
• Principal Investigator: MORI Masaki 九州大学, 医学研究院, 教授 (70190999)
• Co-Investigator(Kenkyū-buntansha): 土岐 祐一郎 大阪大学, 医学系研究科, 教授 (20291445) ; 永野 浩昭 山口大学, 大学院医学系研究科, 教授 (10294050) ; 石井 秀始 大阪大学, 医学系研究科, 特任教授(常勤) (10280736) ; 三森 功士 九州大学, 大学病院, 教授 (50322748) ; 杉本 昌弘 慶應義塾大学, 政策・メディア研究科(藤沢), 特任教授 (30458963) ; 落谷 孝広 国立研究開発法人国立がん研究センター, 研究所, プロジェクトリーダー (60192530)
• Project Period (FY): 2015-05-29 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥199,940,000 (Direct Cost: ¥153,800,000、Indirect Cost: ¥46,140,000); Fiscal Year 2019: ¥38,610,000 (Direct Cost: ¥29,700,000、Indirect Cost: ¥8,910,000); Fiscal Year 2018: ¥37,960,000 (Direct Cost: ¥29,200,000、Indirect Cost: ¥8,760,000); Fiscal Year 2017: ¥39,130,000 (Direct Cost: ¥30,100,000、Indirect Cost: ¥9,030,000); Fiscal Year 2016: ¥40,950,000 (Direct Cost: ¥31,500,000、Indirect Cost: ¥9,450,000); Fiscal Year 2015: ¥43,290,000 (Direct Cost: ¥33,300,000、Indirect Cost: ¥9,990,000)
• Keywords: 早期膵癌 / 遺伝子多型 / 環境 / バイオマーカー / 腫瘍遺伝子 / 膵癌 / 先制医療 / 癌代謝 / 環境因子 / 遺伝子的多型因子 / 先端計測 / ﾊﾞｲｵﾏｰｶｰ

Outline of Final Research Achievements

In this study, we constructed a network of high-volume centers (21 facilities) nationwide, and collected clinical samples of early (stage I) pancreatic cancer patients that were extremely difficult to diagnose. Using these samples, we developed a new diagnostic method for early detection of pancreatic cancer. As the results, we showed that the methylation rate of microRNAs in peripheral blood was elevated and that the amount of two metabolites in saliva were significantly increased. We also identified polymorphisms characteristic of Japanese pancreatic cancer patients. These methods can serve as a platform for diagnosing early pancreatic cancer with high accuracy, and are expected to contribute to a dramatic reduction in mortality due to pancreatic cancer.

Academic Significance and Societal Importance of the Research Achievements

これまで早期癌の状態で発見することが難しく、それゆえに研究するための検体や臨床情報すら不足していたステージI膵癌の臨床像、遺伝子／蛋白発現プロファイルが明らかになった。また、低侵襲で正確に早期膵癌を診断する方法を樹立することができ、本方法をさらに実臨床で検証すれば、本研究の成果が膵癌の早期発見と予後改善に寄与出来るものと期待される。

Assessment Rating

Verification Result (Rating)

A-

Research Products

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  • Peer Reviewed / Open Access
• [Journal Article] Pancreatic cancer immunotherapy using a tumor lysate vaccine, engineered to express α-gal epitopes, targets pancreatic cancer stem cells. (2015)
  • Author(s): Tanida, T., Tanemura, M., Miyoshi, E., Nagano, H., Furukawa, K., Nonaka, Y., Akita, H., Hama, N., Wada, H., Kawamoto, K., Kobayashi, S., Eguchi, H., Mori, M., Doki, Y.
  • Journal Title: Int. J. Oncol. Volume: 46 Issue: 1 Pages: 78-90
  • DOI: 10.3892/ijo.2014.2717
  • Peer Reviewed / Open Access
• [Journal Article] Efficacy of preoperative dexamethasone for postoperative nausea and vomiting after laparoscopic cholecystectomy: a large-scale, multicenter, randomized, double-blind, placebo-controlled trial in Japan. (2015)
  • Author(s): Wakasugi, M., Tori, M., Shimizu, J., Kim, YK., Noda, T., Dono, K., Takeda, Y., Yamamoto, T., Oshima, S., Morimoto, Y., Asaoka, T., Eguchi, H., Nagano, H., Mori, M., Doki, Y.
  • Journal Title: J. Hepatobiliary. Pancreat. Sci. Volume: 22 Issue: 11 Pages: 802-809
  • DOI: 10.1002/jhbp.285
  • Peer Reviewed / Open Access
• [Journal Article] The combination of the expression of hexokinase 2 and pyruvate kinase M2 is a prognostic marker in patients with pancreatic cancer. (2015)
  • Author(s): Ogawa, H., Nagano, H., Konno, M., Eguchi, H., Koseki, J., Kawamoto, K., Nishida, N., Colvin, H., Tomokuni, A., Tomimaru, Y., Hama, N., Wada, H., Marubashi, S., Kobayashi, S., Mori, M., Doki, Y., Ishii, H.
  • Journal Title: Mol. Clin. Oncol. Volume: 3 Pages: 563-571
  • Peer Reviewed / Open Access
• [Journal Article] Implications of peritoneal lavage cytology in resectable left-sided pancreatic cancer. (2015)
  • Author(s): Iwagami, Y., Eguchi, H., Wada, H., Tomimaru, Y., Hama, N., Kawamoto, K., Kobayashi, S., Mori, M., Doki,Y., Nagano, H.
  • Journal Title: Surg, Today. Volume: 45 Issue: 4 Pages: 444-450
  • DOI: 10.1007/s00595-014-0964-7
  • Peer Reviewed / Open Access
• [Journal Article] F-box protein FBXW7 inhibits cancer metastasis in a non-cell-autonomous manner (2015)
  • Author(s): Yumimoto, K., Akiyoshi, S., Ueo, H., Sagara, Y., Onoyama, I., Ueo, H., Ohno, S., Mori, M., Mimori, K., Nakayama, K. I.
  • Journal Title: J. Clin. Invest. Volume: 125 Issue: 2 Pages: 621-635
  • DOI: 10.1172/jci78782
  • Peer Reviewed / Open Access
• [Presentation] 消化器癌領域における指針の医療研究開発 (2016)
  • Author(s): 森正樹、石岡千加史
  • Organizer: 第75回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜(神奈川）
  • Year and Date: 2016-10-06
• [Presentation] リキッドバイオプシー 最近の動向 (2016)
  • Author(s): 森正樹
  • Organizer: 第75回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜(神奈川）
  • Year and Date: 2016-10-06
• [Presentation] 未来へつなぐ消化器病学―消化器外科の立場から― (2016)
  • Author(s): 森正樹
  • Organizer: 第102回日本消化器病学会総会
  • Place of Presentation: 京王プラザホテル(東京）
  • Year and Date: 2016-04-21
• [Presentation] マイクロRNA導入による難治性癌の克服 (2015)
  • Author(s): 森正樹、石井秀始、浜部敦史、今野雅允、長谷川慎一郎、江口英利、土岐祐一郎
  • Organizer: 第53回日本癌治療学会学術集会
  • Place of Presentation: 国立京都国際会館(京都）
  • Year and Date: 2015-10-29
• [Presentation] 肉眼的脈管侵襲や遠隔転移を伴った進行肝細胞癌（BCLC advanced stage）に対する肝切除術の適応 (2015)
  • Author(s): 和田浩志、江口英利、富丸慶人、友國晃、浅岡忠史、川本弘一、丸橋繁、梅下浩司、土岐祐一郎、森正樹、永野浩昭
  • Organizer: 第51回日本肝癌研究会
  • Place of Presentation: 神戸国際会議場(兵庫）
  • Year and Date: 2015-07-23
• [Presentation] 高度脈管侵襲を伴った進行肝細胞癌に対する肝切除を基軸とした治療戦略 (2015)
  • Author(s): 和田浩志、江口英利、富丸慶人、友國晃、浅岡忠史、川本弘一、丸橋繁、梅下浩司、土岐祐一郎、森正樹、永野浩昭
  • Organizer: 第27回日本肝胆膵外科学会・学術集会
  • Place of Presentation: ホテル グランパシフィック LE DAIBA (東京）
  • Year and Date: 2015-06-11