Molecular signature-based classification of circulating tumor cells and its clinical application for refinement of multidisciplinary treatment of pancreatic cancer.
Project/Area Number |
19K09209
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 55020:Digestive surgery-related
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Research Institution | Yamagata University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
古川 徹 東北大学, 医学系研究科, 教授 (30282122)
畠 達夫 東北大学, 医学系研究科, 大学院非常勤講師 (30806237)
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Project Period (FY) |
2019-04-01 – 2022-03-31
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Project Status |
Completed (Fiscal Year 2021)
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Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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Keywords | 膵癌 / 血中循環腫瘍細胞 / 循環腫瘍細胞 / プレシジョン医療 / 集学的治療 |
Outline of Research at the Start |
切除を企図した膵癌の集学的治療にリキッドバイオプシーに基づいたプレシジョン医療を導入することが重要である。本研究は、マルチカラー解析と陽性細胞を繰り返しソートする純化技術を用いて血中循環腫瘍細胞(CTC)を高精度に単離することで、これまでの報告にはない、発現マーカーに基づくCTCのサブタイプ分類とそれぞれの変異、発現、パスウェイなどの特徴、いわゆる分子署名を明らかにすることを目的とし、更に分子署名から創出されたバイオマーカーの有用性を微小転移診断、治療効果予測、病勢モニタリングなどの点から明らかにし、将来的なプレシジョン医療の具現化への橋渡しを目指す。
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Outline of Final Research Achievements |
In pancreatic cancer, tumor-derived DNA (ctDNA) is more easily detected in the peritoneal washing fluid than in the peripheral blood, and CY ctDNA-positive cases have a significantly poorer prognosis than negative cases, suggesting that CY ctDNA is a useful biomarker reflecting minimal residual disease. Exosomes were isolated from CY and analyzed for exosomal protein markers. miRNA was also extracted and its expression was examined using digital PCR, and miR-21 was found to be more highly expressed in the CY-positive group. Exosome fractions contain consentrated tumor-derived nucleic acids (DNA&RNA) and should be evaluated for useful samples.
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Academic Significance and Societal Importance of the Research Achievements |
既知の腫瘍マーカーが全ての膵癌症例のおいてその病勢を正確に反映しているとは限らないため、微小転移診断、治療効果予測、病勢モニタリングなどの用途に応じた、より高精度なバイオマーカーの同定・開発が求められる。本研究では、通常診療で侵襲なく得られる腹腔洗浄液により、得られたサンプルがバイオマーカーとして介入法決断・予後予測に有用である可能性を示唆した。難治癌の代表である膵癌診断・治療技術の進歩に寄与できた。
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Report
(4 results)
Research Products
(14 results)
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[Journal Article] Impact of Tumor-Derived DNA Testing in Peritoneal Lavage of Pancreatic Cancer Patients with and Without Occult Intra-Abdominal Metastases.2022
Author(s)
Chiba K, Hata T, Mizuma M, Masuda K, Aoki S, Takadate T, Kawaguchi K, Nakagawa K, Morikawa T, Motoi F, Furukawa T, Unno M.
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Journal Title
Ann Surg Oncol.
Volume: 29
Issue: 4
Pages: 2685-2697
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Serum Anti-p53 Antibody Can Serve as a Predictive Marker for Histological Grade of Intraductal Papillary Mucinous Neoplasms of the Pancreas.2020
Author(s)
Hata T, Mizuma M, Motoi F, Iseki M, Omori Y, Hayashi H, Nakagawa K, Morikawa T, Kamei T, Naitoh T, Furukawa T, Unno M.
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Journal Title
Pancreas.
Volume: 49
Issue: 6
Pages: 768-773
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Prognostic impact of intraoperative peritoneal cytology after neoadjuvant therapy for potentially resectable pancreatic cancer.2020
Author(s)
Aoki S, Mizuma M, Hayashi H, Yoshimachi S, Hata T, Miura T, Takadate T, Maeda S, Ariake K, Kawaguchi K, Masuda K, Ishida M, Ohtsuka H, Nakagawa K, Morikawa T, Motoi F, Unno M.
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Journal Title
Pancreatology.
Volume: 20
Issue: 8
Pages: 1711-1717
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] GNAS mutation detection in circulating cell-free DNA is a specific predictor for intraductal papillary mucinous neoplasms of the pancreas, especially for intestinal subtype.2020
Author(s)
Hata T, Mizuma M, Motoi F, Omori Y, Ishida M, Nakagawa K, Hayashi H, Morikawa T, Kamei T, Furukawa T, Unno M.
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Journal Title
Sci Rep.
Volume: 10
Issue: 1
Pages: 17761-17761
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] 初診時切除不能膵癌に対する非手術療法奏効後切除の前向き観察研究:Prep042021
Author(s)
元井冬彦, 中森正二, 松本逸平, 里井壯平, 平野聡, 川畑康成, 庄雅之, 本田五郎, 木村康利, 岸和田昌之, 青笹季文, 岡野圭一, 北川裕久, 村上義昭, 海野倫明
Organizer
第51回日本膵臓学会大会
Related Report
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