Investigation of the pathogenesis of gastrointestinal tract neuroendocrine carcinoma through microscaled proteogenomic analysis
Project/Area Number |
20K17069
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 53010:Gastroenterology-related
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Research Institution | National Cancer Center Japan |
Principal Investigator |
Hirano Hidekazu 国立研究開発法人国立がん研究センター, 中央病院, 医員 (30796800)
|
Project Period (FY) |
2020-04-01 – 2023-03-31
|
Project Status |
Completed (Fiscal Year 2022)
|
Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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Keywords | 消化管原発神経内分泌がん / プロテオゲノミクス解析 / プロテオゲノミクス / 消化管神経内分泌癌 / 消化管原発神経内分泌癌 / 微量検体 |
Outline of Research at the Start |
【研究目的】 希少かつ難治性がんである消化管原発神経内分泌癌(GI-NEC)の個別化医療の確立を目指して、生理的かつ経時的評価が可能な内視鏡生検検体による高感度プロテオゲノミクス解析技術を構築し、GI-NECの疾患メカニズムを解明する。 【研究目標】 I. GI-NECの内視鏡生検検体を用いる高感度プロテオゲノミクス解析基盤の開発 II. GI-NECの分子生物学的特性の解明および新規治療標的分子の探索
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Outline of Final Research Achievements |
Using endoscopic biopsy specimens collected from primary tumors of patients with untreated gastrointestinal tract neuroendocrine carcinomas (GI-NECs), genomic profiling tests, proteomic analysis, and phosphoproteomic analysis were performed to investigate abnormalities in biological functions in GI-NECs. Proteomic and phosphoproteomic analysis revealed the activation of signaling and kinases of the cell cycle and DNA repair mechanisms in tumor tissues compared with non-tumor adjacent tissues. Proteomic and phosphoproteomic analysis provided information that is difficult to be acquired by genomic profiling tests, suggesting the importance of proteogenomic analysis in elucidating the disease mechanism and exploring novel therapeutic targets in GI-NECs.
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Academic Significance and Societal Importance of the Research Achievements |
消化管原発神経内分泌癌は予後不良な希少がんであり、切除可能性に関わらず新規治療開発が求められている。また、その希少性から、分子学的異常に基づく治療法の確立がされておらず、アンメットニーズが高い疾患である。本研究は、消化管原発神経内分泌癌におけう微量生検検体によるプロテオゲノミクス解析の有用性を示すものであり、研究の蓄積による今後の臨床応用が期待される。
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Report
(4 results)
Research Products
(7 results)
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[Journal Article] Integration of pharmacoproteomic and computational approaches reveals the cellular signal transduction pathways affected by apatinib in gastric cancer cell lines2023
Author(s)
Nojima Y, Aoki M, Re S, Hirano H, Abe Y, Narumi R, Muraoka S, Shoji H, Honda K, Tomonaga T, Mizuguchi K, Boku N, Adachi J.
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Journal Title
Comput Struct Biotechnol J.
Volume: Mar 15;21
Pages: 2172-2187
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Temporal dynamics from phosphoproteomics using endoscopic biopsy specimens provides new therapeutic targets in stage IV gastric cancer2022
Author(s)
Hirano H, Abe Y, Nojima Y, Aoki M, Shoji H, Isoyama J, Honda K, Boku N, Mizuguchi K, Tomonaga T, Adachi J.
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Journal Title
Sci Rep.
Volume: 12(1)
Issue: 1
Pages: 4419-4419
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] StageIV胃癌における内視鏡生検検体を用いた経時的リン酸化プロテオーム解析による新規治療標的の探索2022
Author(s)
Hirano H, Abe Y, Nojima Y, Aoki M, Shoji H, Isoyama J, Honda K, Boku N, Mizuguchi K, Tomonaga T, Adachi J.
Organizer
日本分子腫瘍マーカー研究会
Related Report
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[Presentation] Temporal dynamics of phosphoproteomics using endoscopic biopsy specimens in stage IV gastric cancer2022
Author(s)
Hirano H, Abe Y, Nojima Y, Aoki M, Shoji H, Isoyama J, Honda K, Boku N, Mizuguchi K, Tomonaga T, Adachi J.
Organizer
日本胃癌学会総会
Related Report
Int'l Joint Research
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[Presentation] Temporal dynamics of phosphoproteomics using endoscopic biopsy specimens in stage IV gastric cancer2022
Author(s)
Hidekazu Hirano, Yuichi Abe, Yosui Nojima, Masahiko Aoki, Hirokazu Shoji, Junko Isoyama, Kazufumi Honda, Narikazu Boku, Kenji Mizuguchi, Takeshi Tomonaga, Jun Adachi
Organizer
第94回日本胃癌学会
Related Report
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