2023 Fiscal Year Final Research Report

Possible treatment strategy of one-carbon metabolism on pancreatic cancer management

Research Project

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Project/Area Number	21K07147
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 50010:Tumor biology-related
Research Institution	Nagoya University
Principal Investigator	HAYASHI Masamichi 名古屋大学, 医学部附属病院, 講師 (70755503)
Co-Investigator(Kenkyū-buntansha)	小寺泰弘名古屋大学, 医学系研究科, 教授 (10345879) 猪川祥邦名古屋大学, 医学部附属病院, 病院講師 (80772863) 檜顕成名古屋大学, 医学系研究科, 特任教授 (90383257)
Project Period (FY)	2021-04-01 – 2024-03-31
Keywords	膵癌 / one carbon metabolism / メチル化 / 葉酸
Outline of Final Research Achievements	We initially examined the Folate and s-adenosylmethionine (SAM) concentrations in preoperative serum samples from 32 pancreatic cancer cases. High folate cases showed less frequent lymphatic node metastasis and relatively favorable postoperative survival outcomes. High SAM cases were found in pancreatic head cancers and were relatively sensitive to preoperative chemotherapy. Next, we checked whether the one carbon metabolism cycle is downregulated in 37 preoperative pancreatic cancer cases compared with 25 healthy control cases by LC/MS data of their urine samples. Concentrations of choline, betaine, methionine, SAM and s-adenosylhomocysteine were concordantly downregulated in cancer cases, which implies that weakened one-carbon metabolism may cause carcinogenesis or enhance cancer malignant potentials.
Free Research Field	消化器外科学
Academic Significance and Societal Importance of the Research Achievements	膵癌治療はいまだ発展途上にあり、また罹患率も確実に上昇傾向にある。その早期発見の困難さゆえに、手術を含めた集学的治療を行っても治癒困難な難治癌と呼ばれて久しい。そこで、発癌進行メカニズムについての新知見に基づいた新規治療の開発が必要と考え、今回one carbon metabolismの観点から膵癌症例、予後不良症例の特徴を検討した。膵癌症例の術前血清検体、尿検体を用いた検討では、Folateやs-adenosylmethionineの含有量低下がone carbon metabolism回路の活性低下をきたし、膵癌発癌や癌進行に寄与している可能性が示唆された。