Digiral PCR-based plasma cell-free DNA mutation analysis for early-stage pancreatic tumor diagnosis and surveillance （デジタルPCRを用いた遺伝子変異解析による膵腫瘍の早期診断とサーベイランス）

• Material Type: 博士論文
• ISSN: 0944-1174
• Title: Digiral PCR-based plasma cell-free DNA mutation analysis for early-stage pancreatic tumor diagnosis and surveillance （デジタルPCRを用いた遺伝子変異解析による膵腫瘍の早期診断とサーベイランス）
• Volume: 55 12
• Author/Editor: 岡田, 哲弘
• Author Heading: 岡田, 哲弘
• Publication Date: 2020-12; 55 12
• Publication Date (W3CDTF): 2020-12
• Periodical title: Journal of gastroenterology
• Degree grantor/type: 旭川医科大学
• Date Granted: 2021-03-25
• Date Granted (W3CDTF): 2021-03-25
• Dissertation Number: 甲第555号
• Degree Type: 博士（医学）
• Conferring No. (Dissertation): 甲第555号
• Text Language Code: eng
• Subject Heading: Cell-free DNA; Digital PCR; Liquid biopsy; Pancreatic cancer; Risk assessment
• Target Audience: 一般
• Note (General): type:application/pdf; Background: Cell-free DNA (cfDNA) shed from tumors into the circulation offers a tool for cancer detection. Here, we evaluated the feasibility of cfDNA measurement and utility of digital PCR (dPCR)-based assays, which reduce subsampling error, for diagnosing pancreatic ductal adenocarcinoma (PDA) and surveillance of intraductal papillary mucinous neoplasm (IPMN).Methods: We collected plasma from seven institutions for cfDNA measurements. Hot-spot mutations in KRAS and GNAS in the cfDNA from patients with PDA (n = 96), undergoing surveillance for IPMN (n = 112), and normal controls (n = 76) were evaluated using pre-amplification dPCR.Results: Upon Qubit measurement and copy number assessment of hemoglobin-subunit (HBB) and mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 1 (MT-ND1) in plasma cfDNA, HBB offered the best resolution between patients with PDA relative to healthy subjects [area under the curve (AUC) 0.862], whereas MT-ND1 revealed significant differences between IPMN and controls (AUC 0.851). DPCR utilizing pre-amplification cfDNA afforded accurate tumor-derived mutant KRAS detection in plasma in resectable PDA (AUC 0.861-0.876) and improved post-resection recurrence prediction [hazard ratio (HR) 3.179, 95% confidence interval (CI) 1.025-9.859] over that for the marker CA19-9 (HR 1.464; 95% CI 0.674-3.181). Capturing KRAS and GNAS could also provide genetic evidence in patients with IPMN-associated PDA and undergoing pancreatic surveillance.Conclusions: Plasma cfDNA quantification by distinct measurements is useful to predict tumor burden. Through appropriate methods, dPCR-mediated mutation detection in patients with localized PDA and IPMN likely to progress to invasive carcinoma is feasible and complements conventional biomarkers.
• DOI: info:doi/10.1007/s00535-020-01724-5; https://doi.org/info:doi/10.1007/s00535-020-01724-5
• Persistent ID (NDL): info:ndljp/pid/11929635; https://dl.ndl.go.jp/pid/11929635
• Collection (particular): 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• Acquisition Basis: 博士論文（自動収集）
• Date Accepted (W3CDTF): 2021-12-07T08:33:55+09:00
• Format (IMT): application/pdf
• Access Restrictions: 国立国会図書館内限定公開
• Service for the Digitized Contents Transmission Service: 図書館・個人送信対象外
• Availability of remote photoduplication service: 可
• Periodical Title (URI): https://amcor.asahikawa-med.ac.jp/modules/xoonips/detail.php?id=20210325_K555
• Data Provider (Database): 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp