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Serum CA19–9, cathepsin D, and matrix metalloproteinase-7 as a diagnostic panel for pancreatic ductal adenocarcinoma

Authors

  • Hyung-Doo Park,

    1. Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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  • Eun-Suk Kang,

    1. Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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  • Jong-Won Kim,

    1. Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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  • Kyu-Taek Lee,

    1. Division of Gastroenterology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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  • Kwang Hyuck Lee,

    1. Division of Gastroenterology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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  • Young Suk Park,

    1. Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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  • Joon-Oh Park,

    1. Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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  • Jeeyun Lee,

    1. Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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  • Jin Seok Heo,

    1. Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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  • Seong Ho Choi,

    1. Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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  • Dong Wook Choi,

    1. Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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  • Seonwoo Kim,

    1. Department of Biostatistics, Samsung Biomedical Research Institute, Seoul, Korea
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  • Jong Kyun Lee,

    Corresponding author
    1. Division of Gastroenterology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
    • Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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  • Soo-Youn Lee

    Corresponding author
    1. Department of Clinical Pharmacology and Therapeutics, Samsung Medical Center, Seoul, Korea
    • Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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Correspondence: Professor Soo-Youn Lee, Department of Laboratory Medicine and Genetics, Samsung Medical Center, 50 Irwon-dong, Gangnam-gu, Seoul, 135-710, Korea

E-mail: suddenbz@skku.edu

Fax: +82-2-3410-2719

Additional corresponding author: Professor Jong Kyun Lee, E-mail: jongk.lee@samsung.com

Abstract

Pancreatic ductal adenocarcinoma (PDAC) accounts for 95% of pancreatic cancers. CA19-9 is not widely used for screening PDAC due to its low sensitivity. Here, we studied the clinical usefulness of cathepsin D, matrix metalloproteinases (MMPs), and tissue inhibitors of MMPs (TIMPs) for screening patients with PDAC. A total of 248 patients with PDAC and 216 control subjects were recruited (109 PDAC patients and 70 controls in the training set and 139 PDAC patients and 146 controls in the validation set). We measured serum levels of cathepsin D, TIMPs (−1, −3, and −4), and MMPs (−1, −7, −8, and −9) using Fluorokine MAP multiplex kits. The concentrations of cathepsin D and MMP-7 were significantly higher in PDAC subjects than control subjects. In the training set, the diagnostic sensitivity and AUC of the panel of CA19-9, cathepsin D, and MMP-7 for PDAC were increased to 88% and 0.900, compared to 74% and 0.835 of CA19-9 single marker at 80% specificity. The sensitivity using cut-off value of biomarker panel was significantly increased in the validation set as well as training set. Our findings indicate that a serum biomarker panel consisting of CA19-9, cathepsin D, and MMP-7 may provide the most effective screening test currently feasible for PDAC.

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