Exploratory analysis of DNA methylation as a novel biomarker in gastrointestinal cancer chemotherapy

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K08328
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Nagoya University
• Principal Investigator: Maeda Osamu 名古屋大学, 医学部附属病院, 病院准教授 (20378053)
• Co-Investigator(Kenkyū-buntansha): 近藤 豊 名古屋大学, 医学系研究科, 教授 (00419897) ; 安藤 雄一 名古屋大学, 医学部附属病院, 教授 (10360083) ; 藤城 光弘 名古屋大学, 医学系研究科, 教授 (70396745) ; 古川 和宏 名古屋大学, 医学系研究科, 講師 (70624310)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: DNAメチル化 / 循環腫瘍DNA / 食道癌 / 胃癌 / がん化学療法

Outline of Final Research Achievements

DNA and RNA were extracted from tumor samples from esophageal and gastric cancers undergoing chemotherapy, and tumor-derived circulating DNA was extracted from blood samples. Comprehensive analysis of gene mutation, gene expression, and DNA methylation was performed. Methylation levels of blood-derived ctDNA before and after chemotherapy with cisplatin and fluorouracil for 185 genes whose DNA methylation was altered in the anti-cancer drug-resistant cell lines, SPTSSB increased and CD81 and FASTK decreased after chemotherapy, which were consistent with the changes seen in the anti-cancer drug-resistant cell lines. The changes were consistent with those seen in anticancer drug-resistant cell lines. The results suggest that changes in DNA methylation levels associated with anticancer drug resistance may also be detectable in ctDNA.

Free Research Field

がん薬物療法

Academic Significance and Societal Importance of the Research Achievements

化学療法施行中に繰り返し腫瘍組織を採取することは一般的には多くないが、食道がんや胃がんは、がん薬物療法の経過中に、原発巣の縮小効果判定のために消化管内視鏡検査と生検を行い、繰り返し腫瘍組織を採取することがある。腫瘍検体と血液から得られる腫瘍由来のctDNAを用いて、がん薬物療法の効果とctDNAのメチル化の関連を評価した。腫瘍とctDNAのメチル化、さらに薬剤感受性の関連を解析することによって、より低侵襲の最適ながん薬物療法の選択法を開発できる可能性が示唆された。