Construction of innovative preemptive medicine for gastrointestinal cancer especially including pancreatic cancer

• Project/Area Number: 18K18464
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Studies on the Super-Aging Society
• Research Institution: Kawasaki Medical School
• Principal Investigator: NAGASAKA TAKESHI 川崎医科大学, 医学部, 准教授 (30452569)
• Co-Investigator(Kenkyū-buntansha): 山口 佳之 川崎医科大学, 医学部, 教授 (10230377) ; 楳田 祐三 岡山大学, 大学病院, 講師 (10573735) ; 堅田 洋佑 川崎医科大学, 医学部, 助教 (20716881) ; 母里 淑子 岡山大学, 大学病院, 助教 (70708081)
• Project Period (FY): 2018-06-29 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000); Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2019: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 腫瘍検査学 / 検査・診断システム / 生体情報・計測 / 健康情報 / 超高齢社会研究

Outline of Final Research Achievements

In the aging society of developed countries, the morbidity of malignant tumors suddenly destroys the "healthy life expectancy". This means, even in a state where one can live independently in a social life, the end of life will come along with the burden close to despair mentally, physically and economically.　However, if gastrointestinal cancer can be detected at early phase, could being fully cured.
In this study, we showed that abnormal methylation is a universal alteration regardless of the type of cancer and possible to screen gastrointestinal cancer in general, including pancreatic cancer, by detecting fecal DNA methylation. For high-risk people with malignancy, continuously detecting fecal DNA methylation could predict in the early stage of onset without any abnormalities in other laboratory findings with extremely minimally invasive, thus lading the foundation for innovative preemptive medicine that enables.

Academic Significance and Societal Importance of the Research Achievements

本研究結果により、メチル化異常が癌種に関係なく、普遍的に認められる変化であることが示唆され、適切なバイオマーカー選択により、大腸癌、IPMN、食道癌、胃癌、膵癌、十二指腸癌、胆管癌といった悪性腫瘍群と非担癌群を選別することが可能であることが示された。これら結果から、担癌高リスク者に対し、極めて低侵襲である便中メチル化DNA検出を継続的に行うことにより、検査所見でも異常のない発症前期に膵癌・消化器癌を診断・予測し、薬剤投与等による化学予防 (Chemoprevention) を可能にする革新的な先制医療 (Preemptive Medicine) の構築が可能となると確信している。

Research Products

• [Journal Article] Lower incidence of adverse events about capecitabine and oxaliplatin from the GOIM 2802 study: a commentary (2020)
  • Author(s): Tanioka, H. Nagasaka, T.
  • Journal Title: Digestive Medicine Research Volume: ３ Pages: 1-5
  • DOI: 10.21037/dmr-20-100
  • Peer Reviewed / Open Access
• [Journal Article] The PVT1 lncRNA is a novel epigenetic enhancer of MYC, and a promising risk-stratification biomarker in colorectal cancer (2020)
  • Author(s): Shigeyasu, K. Toden, S. Ozawa, T. Matsuyama, T. Nagasaka, T. Ishikawa, T. Sahoo, D. Ghosh, P. Uetake, H. Fujiwara, T. Goel, A.
  • Journal Title: Mol Cancer Volume: 1 Issue: 1 Pages: 155-155
  • DOI: 10.1186/s12943-020-01277-4
  • Peer Reviewed / Open Access
• [Journal Article] [A New Era of Colorectal Cancer Treatment Being Led by a Precise Analysis of Somatic Mutational Profiles Including RAS, BRAF Mutation and Microsatellite Instability Status] (2020)
  • Author(s): Nagasaka, T.
  • Journal Title: Gan To Kagaku Ryoho Volume: 47 Pages: 861-869
• [Journal Article] Upregulation of microRNA?31 is associated with poor prognosis in patients with advanced colorectal cancer (2020)
  • Author(s): Kubota Nobuhito、Taniguchi Fumitaka、Nyuya Akihiro、Umeda Yuzo、Mori Yoshiko、Fujiwara Toshiyoshi、Tanioka Hiroaki、Tsuruta Atsushi、Yamaguchi Yoshiyuki、Nagasaka Takeshi
  • Journal Title: Oncology Letters Volume: 19（４） Pages: 2685-2694
  • DOI: 10.3892/ol.2020.11365
  • Peer Reviewed / Open Access
• [Journal Article] Natural history of epithelioid hemangioendothelioma that progressed over 20 years (2020)
  • Author(s): Imashuku, S. Hashikura, H. Nagasaka, T.
  • Journal Title: Pediatr Blood Cancer Volume: 67 Issue: 6
  • DOI: 10.1002/pbc.28261
  • Peer Reviewed / Open Access
• [Journal Article] Molecular Characterization of Second Primary Endometrial Cancer (2020)
  • Author(s): HARAGA JUNKO、NAKAMURA KEIICHIRO、HARUMA TOMOKO、NYUYA AKIHIRO、NAGASAKA TAKESHI、MASUYAMA HISASHI
  • Journal Title: Anticancer Research Volume: 40 Issue: 7 Pages: 3811-3818
  • DOI: 10.21873/anticanres.14370
  • Peer Reviewed / Open Access
• [Journal Article] ある大腸癌の物語 (2020)
  • Author(s): 永坂岳司
  • Journal Title: W'Waves 日本癌病態治療研究会誌 Volume: 26(1) Pages: 28-34
• [Journal Article] 特集 FIT陰性癌の特徴 話題提供 FIT vs. 便中DNA検査 (2019)
  • Author(s): 永坂岳司
  • Journal Title: INTESTINE Volume: 23（５） Pages: 462-465
• [Journal Article] Heterogeneity of Epigenetic and Epithelial Mesenchymal Transition Marks in Hepatocellular Carcinoma with Keratin 19 Proficiency (2018)
  • Author(s): Yokomichi Naosuke、Nishida Naoshi、Umeda Yuzo、Taniguchi Fumitaka、Yasui Kazuya、Toshima Toshiaki、Mori Yoshiko、Nyuya Akihiro、Tanaka Takehiro、Yamada Takeshi、Yagi Takahito、Fujiwara Toshiyoshi、Yamaguchi Yoshiyuki、Goel Ajay、Kudo Masatoshi、Nagasaka Takeshi
  • Journal Title: Liver Cancer Volume: none Issue: 4 Pages: 1-16
  • DOI: 10.1159/000490806
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Antitumor activity of pan-HER inhibitors in HER2-positive gastric cancer. (2018)
  • Author(s): Yoshioka T, Shien K, Namba K, Torigoe H, Sato H, Tomida S, Yamamoto H, Asano H, Soh J, Tsukuda K, Nagasaka T, Fujiwara T, Toyooka S.
  • Journal Title: Cancer Sci. Volume: 109 Issue: 4 Pages: 1166-1176
  • DOI: 10.1111/cas.13546
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Novel evidence for a PIWI-interacting RNA (piRNA) as an oncogenic mediator of disease progression, and a potential prognostic biomarker in colorectal cancer (2018)
  • Author(s): Weng Wenhao、Liu Na、Toiyama Yuji、Kusunoki Masato、Nagasaka Takeshi、Fujiwara Toshiyoshi、Wei Qing、Qin Huanlong、Lin Haifan、Ma Yanlei、Goel Ajay
  • Journal Title: Molecular Cancer Volume: 17 Issue: 1
  • DOI: 10.1186/s12943-018-0767-3
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Accuracy of four mononucleotide-repeat markers for the identification of DNA mismatch-repair deficiency in solid tumors (2018)
  • Author(s): Takehara Y, Nagasaka T, Nyuya A, Haruma T, Haraga J, Mori Y, Nakamura K, Fujiwara T, Boland CR, Goel A.
  • Journal Title: J Transl Med. Volume: 16 Issue: 1 Pages: 5-5
  • DOI: 10.1186/s12967-017-1376-4
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] [Analysis of Fecal Cancer-Specific DNA to Detect Colorectal Neoplasia] (2018)
  • Author(s): Nagasaka, T. Yamaguchi, Y.
  • Journal Title: Gan To Kagaku Ryoho Volume: 45 Pages: 906-910
• [Journal Article] Clinical outcomes of women with ovarian metastases of colorectal cancer treated with oophorectomy with respect to their somatic mutation profiles. (2018)
  • Author(s): Mori Y, Nyuya A, Yasui K, Toshima T, Kawai T, Taniguchi F, Kimura K, Inada R, Nishizaki M, Haraga J, Nakamura K, Umeda Y, Kishimoto H, Fujiwara T, Katata Y, Yamaguchi Y, Nagasaka T.
  • Journal Title: Oncotarget Volume: 27;9(23) Issue: 23 Pages: 16477-16488
  • DOI: 10.18632/oncotarget.24735
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Living Donor Liver Transplantation for Acute Liver Failure : Comparing Guidelines on the Prediction of Liver Transplantation. (2017)
  • Author(s): Yoshida K, Umeda Y, Takaki A, Nagasaka T, Yoshida R, Nobuoka D, Kuise T, Takagi K, Yasunaka T, Okada H, Yagi T, Fujiwara T.
  • Journal Title: Acta Med Okayama Volume: 71(5) Pages: 381-390
  • DOI: 10.3892/ol.2017.7553
  • NAID: 120006352357
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 抗VEGF抗体RAMUCIRUMABによる肝転移巣の肝類洞血小板凝集 (2020)
  • Author(s): 永坂岳司, 田中健大, 母里淑子, 谷岡洋亮, 堅田洋佑, 岡脇誠, 佐野史典, 山村真弘, 山口佳之
  • Organizer: 第33回日本バイオセラピィ学会学術集会総会
• [Presentation] Cell-free and concentrated ascites reinfusion therapy (CART)におけるNeutrophil to Lymphocyte Ratioと予後の関係 (2020)
  • Author(s): 岡脇誠, 永坂岳司, 佐野史典, 谷岡洋亮, 堅田洋祐, 山村真弘, 山口佳之
  • Organizer: 第33回日本バイオセラピィ学会学術集会総会
• [Presentation] 切除不能胃癌患者の各治療開始前好中球リンパ球比と抗腫瘍効果の検討：3次治療ニボルマブの抗腫瘍効果を中心に (2020)
  • Author(s): 谷岡洋亮, 永坂岳司, 堅田洋祐, 佐野史典, 岡脇誠, 山村真弘, 山口佳之
  • Organizer: 第33回日本バイオセラピィ学会学術集会総会
• [Presentation] 大腸癌肝転移における抗VEGF抗体による肝類洞血小板凝集効果と肝切除 (2020)
  • Author(s): 永坂岳司, 田中健大, 母里淑子, 谷岡洋亮, 堅田洋佑, 佐野史典, 岡脇誠, 山村真弘, 吉田一博, 重安邦俊, 楳田祐三, 山口佳之
  • Organizer: 第58回日本癌治療学会学術集会
• [Presentation] 進行性消化管間質腫瘍に対するレゴラフェニブ療法により誘発された多形紅斑の2例 (2020)
  • Author(s): 岡脇誠, 永坂岳司, 佐野史典, 谷岡洋亮, 堅田洋祐, 山村真弘, 山口佳之
  • Organizer: 第58回日本癌治療学会学術集会
• [Presentation] 低好中球リンパ球比は胃癌化学療法の良好な抗腫瘍効果の予測因子となりうる (2020)
  • Author(s): 谷岡洋亮, 永坂岳司, 堅田洋祐, 佐野史典, 岡脇誠, 山村真弘, 山口佳之
  • Organizer: 第58回日本癌治療学会学術集会
• [Presentation] 希少がんに対する治療から緩和への流れを再考する(一症例から何が学べるか?) (2020)
  • Author(s): 岡脇誠, 永坂岳司, 佐野史典, 山口佳之
  • Organizer: 第25回日本緩和医療学会学術大会
• [Presentation] Precision Palliative Active Care Programにより最終末期のwell-beingを達成し得た1症例 (2020)
  • Author(s): 高橋誉文, 岡脇誠, 永坂岳司, 佐野史典, 井上明子, 金原唯奈, 出口美穂, 山口 佳之
  • Organizer: 第25回日本緩和医療学会学術大会
• [Presentation] 急性骨髄性白血病・骨髄異形成症候群末期患者の倦怠感に対するステロイドの有用性 (2020)
  • Author(s): 佐野史典, 岡脇誠, 永坂岳司, 山口佳之
  • Organizer: 第25回日本緩和医療学会学術大会
• [Presentation] Genetic Stable胃癌における病理分子生物学的特徴の検討 (2019)
  • Author(s): 谷岡洋亮, 木村圭佑, 入谷光洋, 堅田洋佑, 山口佳之, 永坂岳司
  • Organizer: 第57回日本癌治療学会学術集会
• [Presentation] 抗EGFR抗体によるRAS野生型大腸癌獲得変異に対する検討 (2019)
  • Author(s): 永坂岳司, 入谷光洋, 谷口文崇, 戸嶋俊明, 安井和也, 母里淑子, 楳田祐三, 岸本浩行, 河合毅, 山口佳之
  • Organizer: 第57回日本癌治療学会学術集会
• [Presentation] 血中遊離メチル化 DNA をバイオマーカーに用いた Liquid Biopsy による大腸癌診断の可能性 (2019)
  • Author(s): 永坂岳司, 入谷光洋, 戸嶋俊明, 安井和也, 稲田涼, 母里淑子, 重安邦俊, 楳田祐三, 岸本浩行, 山口佳之
  • Organizer: 第74回日本大腸肛門病学会学術集会
• [Presentation] Genetic 変異情報と Epigenetic 変異情報の融合による新機軸大腸癌 Precision Medicine (2019)
  • Author(s): 永坂岳司, 入谷光洋, 鶴田淳, 渡邊裕策, 峯田修明, 母里淑子, 重安邦俊, 楳田祐三, 岸本浩行, 上野富雄, 山口佳之
  • Organizer: 第74回日本大腸肛門病学会学術集会
• [Presentation] Poor prognosis of hypermutant colorectal cancer with KRAS mutations: A retrospective analysis of 1,052 Japanese colorectal cancer patients without treatment of immuno-checkpoint inhibitors (2019)
  • Author(s): T Nagasaka, H Tanioka, A Nyuya, Y Katata, M Okawaki, M Yamamura, T Kawai, K Yasui, T Toshima, Y Mori, Y Umeda, A Tsuruta, T Ueno, Y Yamaguchi
  • Organizer: World Congress on Gastrointestinal Cancer 2019
  • Int'l Joint Research
• [Presentation] 非侵襲的がん診断システムの開発 (2018)
  • Author(s): 永坂 岳司
  • Organizer: 9th バイオメディカルインターフェイス
• [Presentation] POLE変異大腸癌の臨床病理学的特徴 (2018)
  • Author(s): 永坂 岳司、母里 淑子、入谷 光洋、原賀 順子、重安 邦俊、山村 真弘、堅田 洋佑、谷岡 洋亮、升野 光雄、山口 佳之
  • Organizer: 第63回日本人類遺伝学会
• [Presentation] Lynch 症候群を含むHypermutant 大腸癌における臨床病理学的特徴 (2018)
  • Author(s): 永坂 岳司、母里 淑、鶴田淳、谷岡洋亮、堅田洋佑、重安 邦俊、岸本浩行、矢野修也、戸嶋俊明、 岡脇誠、山村真弘、谷口文崇、楳田祐三、河合毅、河合知則、上野富雄、山口佳之
  • Organizer: 第73回 日本大腸肛門病学会学術集会
• [Presentation] ＰＯＬＥ体細胞変異大腸癌の臨床病理学的特徴 (2018)
  • Author(s): 堅田洋佑、永坂岳司1、入谷光洋、田中健大、河合毅、母里淑子、岡脇誠、山村真弘、谷岡洋亮、山口佳之
  • Organizer: 第29回消化器癌発生学会学術集会
• [Presentation] Distinct Clinico-pathological Features of Hypermutant Colorectal Cancers with POLE Pathogenic Mutations, Lynch Syndrome, or Sporadic MSI over 1,000 colorectal cancer patients’ cohort in Japan. (2018)
  • Author(s): Takeshi Nagasaka, Akihiro Nyuya, Fumitaka Taniguchi, Hiroaki Tanioka, Yosuke Katata, Yoshiko Mori, Takashi Kawai, Makoto Okawaki, Masahiro Yamamura, Yuzo Umeda, Atsushi Turuta, Tomio Ueno, Yoshiyuki Yamaguchi
  • Organizer: ESMO 2018
• [Presentation] Liquid Biopsy has a potential to predict the colorectal cancer patients with destiny for recurrence after curative surgery (2018)
  • Author(s): Toshiaki Toshima, Akihiro Nyuya, Yuzo Umeda, Kazuya Yasui, Kazuhiro Yoshida, Toshiyoshi Fujiwara, Ajay Goel, Takeshi Nagasaka
  • Organizer: ESMO Asia 2018
• [Book] Lynch Syndrome: Molecular Mechanism and Current Clinical Practice 1st ed. 2020 Edition (2020)
  • Author(s): Naohito Tomita
  • Total Pages: 152
  • Publisher: Springer
  • ISBN: 9789811568909