Krebs von den Lungen-6 (KL-6) is a prognostic biomarker in patients with surgically resected nonsmall cell lung cancer

Authors

  • Sonosuke Tanaka,

    1. Department of Molecular and Internal Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8551, Japan
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  • Noboru Hattori,

    Corresponding author
    1. Department of Molecular and Internal Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8551, Japan
    • Department of Molecular and Internal Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan
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    • Tel.: 81-82-257-5196, Fax: 81-82-255-7360

  • Nobuhisa Ishikawa,

    1. Department of Molecular and Internal Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8551, Japan
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  • Hiroyasu Shoda,

    1. Department of Molecular and Internal Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8551, Japan
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  • Atsushi Takano,

    1. Department of Molecular and Internal Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8551, Japan
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  • Ryohei Nishino,

    1. Department of Molecular and Internal Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8551, Japan
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  • Morihito Okada,

    1. Department of Surgical Oncology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8551, Japan
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  • Koji Arihiro,

    1. Department of Anatomical Pathology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8551, Japan
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  • Kouki Inai,

    1. Department of Pathology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8551, Japan
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  • Hironobu Hamada,

    1. Department of Integrated Medicine and Informatics, Ehime University Graduate School of Medicine, Toon, Ehime 791-0295, Japan
    2. Division of Physical Therapy and Occupational Therapy Sciences, Graduate School of Health Sciences, Hiroshima University 734-8551, Hiroshima, Japan
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  • Akihito Yokoyama,

    1. Department of Hematology and Respiratory Medicine, Kochi Medical School, Kochi University, Nankoku, Kochi 783-8505, Japan
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  • Nobuoki Kohno

    1. Department of Molecular and Internal Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8551, Japan
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  • Conflict of Interest: Nobuoki Kohno has a personal royalty of KL-6 from a Japanese pharmaceutical company, Eisai Co., LTD. The remaining authors have no conflicts of interest.

Abstract

By immunizing mice with a lung adenocarcinoma cell line, we previously established a murine IgG1 monoclonal antibody that recognizes a sialylated sugar chain designated Krebs von den Lungen-6 (KL-6). KL-6 is a high–molecular-weight glycoprotein classified as a human MUC1 mucin. The aim of this study was to determine whether KL-6 expression in tumors correlates with circulating KL-6 levels and whether circulating KL-6 has any prognostic value in patients with surgically resected non-small cell lung cancer (NSCLC). Immunohistochemical analysis of KL-6 expression was performed on 103 NSCLC tissues, and its associations with serum KL-6 levels and survival were examined. We also evaluated whether KL-6 expression patterns and/or serum KL-6 levels could predict prognosis in these NSCLC patients. Immunohistochemical analysis of KL-6 in NSCLC tissues showed that a depolarized KL-6 expression pattern was associated with a high level of circulating KL-6 and a poor prognosis in NSCLC patients who underwent curative surgery. Furthermore, a high circulating KL-6 level was associated with both poorer progression-free survival (PFS) and overall survival (OS), and multivariate analyses confirmed its independent prognostic value for both PFS and OS (p = 0.041 and 0.023, respectively). Our data suggest that preoperative serum KL-6 level reflects KL-6 expression patterns in NSCLC tissue, and can serve as a useful prognostic biomarker in NSCLC patients who undergo curative surgery.

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