Investigation of the pathogenesis of gastrointestinal tract neuroendocrine carcinoma through microscaled proteogenomic analysis

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17069
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• 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
• Keywords: 消化管原発神経内分泌がん / プロテオゲノミクス解析

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.

Free Research Field

消化管がんの薬物療法

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。