Development of the novel diagnostic panel by liquid-biopsy for predicting the early-stage pancreatic cancer.

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K16338
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Tohoku University
• Principal Investigator: Hata Tatsuo 東北大学, 医学系研究科, 大学院非常勤講師 (30806237)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 膵癌 / 膵管内乳頭粘液性腫瘍 / リキッドバイオプシー / メチル化DNA / デジタルPCR / 次世代シーケンス

Outline of Final Research Achievements

We focused on the intraductal papillary mucinous neoplasm of the pancreas (IPMN), a major precursor of invasive carcinoma of the pancreas. To identify the diagnostic markers differentiating malignant (high-grade dysplasia with and without invasion) from benign (low-grade dysplasia) IPMN, we revealed the several candidates such as blood based inflammatory markers, nutritional makers, and serum anti-p53 antibody. Furthermore, we performed the droplet digital-PCR (ddPCR) and next generation sequencing and demonstrated the pancreatic cancer associated gene mutations such as TP53, IDH1/2, PTEN, CTNNB1, and SMAD4, all of which were found only in pancraetic cyst fluid obtained from patients with malignant IPMN. Methylated DNA markers were also evaluated by ddPCR using cyst fluids and some potential candidates were identified. In the future, combination assay of these genome and epigenome markers (e.g. development of mini-panel) can contribute to further improvement of diagnostic performance.

Free Research Field

消化器外科学

Academic Significance and Societal Importance of the Research Achievements

本研究の結果をもとに、血液中と嚢胞液中からそれぞれ得られたバイオマーカーを統合・併用することことで、非浸潤性の膵管内乳頭粘液性腺癌の存在を高精度に診断することが可能になる。今後は、膵癌の危険因子である無症候性の膵嚢胞を囲い込んだ上で、さらにこれらのハイリスク例に対して集中的に行うサーベイランスや超音波内視鏡検査などの精査に本研究で得られた診断パネル検査を付随させることで、合理性と実現可能性を兼ね備えた小膵癌の診断バイオマーカーの実現が期待される。