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Digital PCR-based plasma cell-free DNA mutation analysis for early-stage pancreatic tumor diagnosis and surveillance.

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Affiliations

  • 1. Institute of Biomedical Research, Sapporo Higashi Tokushukai Hospital, Sapporo, Japan.
      Authors
    • Okada T 1, 2
    • Mizukami Y 1, 2
    • Ono Y 1, 2
    • Sasajima J 1, 2
    • Taniue K 1
    • Sugitani A 1
    • Karasaki H 1
    (7 authors)
  • 2. Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, 2-1 Midorigaoka Higashi, Asahikawa, Hokkaido, 078-8510, Japan.
      Authors
    • Okada T 1, 2
    • Mizukami Y 1, 2
    • Ono Y 1, 2
    • Sato H 2
    • Hayashi A 2
    • Kawabata H 2
    • Enomoto K 2
    • Goto T 2
    • Sasajima J 1, 2
    • Fujiya M 2
    • Okumura T 2
    (11 authors)
  • 3. Center for Gastroenterology, Shonan Kamakura General Hospital, Kamakura, Japan.
      Authors
    • Koizumi K 3
    • Masuda S 3
    (2 authors)
  • 4. Department of Pathology, Shonan Kamakura General Hospital, Kamakura, Japan.
      Authors
    • Teshima S 4
    (1 author)
  • 5. Center for Gastroenterology, Teine-Keijinkai Hospital, Sapporo, Japan.
      Authors
    • Takahashi K 5
    • Katanuma A 5
    (2 authors)
    • Show all (10)

ORCIDs linked to this article

Journal of Gastroenterology, 16 Sep 2020, 55(12):1183-1193
https://doi.org/10.1007/s00535-020-01724-5 PMID: 32939577 

Abstract 

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.

Full text links 

Read article at publisher's site: https://doi.org/10.1007/s00535-020-01724-5

Read article for free, from open access legal sources, via Unpaywall: https://amcor.asahikawa-med.ac.jp/modules/xoonips/download.php?id=20210325_K555Unpaywall

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Funding 

Funders who supported this work.

JSPS KAKENHI (1)

Japan Society for the Promotion of Science (1)