Detection method for membranous proteins and their utility as a sero-diagnostic markers for lung cancer

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  • Yanagita Kengo
    Department of Molecular Diagnostics, School of Allied Health Sciences, Kitasato University
  • Hagiuda Daisuke
    Department of Applied Tumor Pathology, Graduate School of Medical Sciences, Kitasato University, Kanagawa, Japan
  • Kuchitsu Yuki
    Department of Applied Tumor Pathology, Graduate School of Medical Sciences, Kitasato University, Kanagawa, Japan
  • Inoue Wataru
    Department of Applied Tumor Pathology, Graduate School of Medical Sciences, Kitasato University, Kanagawa, Japan
  • Igawa Satoshi
    Department of Respiratory Medicine, School of Medicine, Kitasato University
  • Ryuge Shinichiro
    Department of Respiratory Medicine, School of Medicine, Kitasato University
  • Saegusa Makoto
    Department of Pathology, School of Medicine, Kitasato University
  • Nagashio Ryo
    Department of Molecular Diagnostics, School of Allied Health Sciences, Kitasato University Department of Applied Tumor Pathology, Graduate School of Medical Sciences, Kitasato University, Kanagawa, Japan
  • Hachimura Kazuo
    Department of Molecular Diagnostics, School of Allied Health Sciences, Kitasato University
  • Sato Yuichi
    Department of Molecular Diagnostics, School of Allied Health Sciences, Kitasato University Department of Applied Tumor Pathology, Graduate School of Medical Sciences, Kitasato University, Kanagawa, Japan

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  • 肺癌における細胞膜タンパク質同定と血清診断マーカーとしての有用性の検討

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<p>To develop novel sero-diagnostic markers for membranous proteins of lung cancer, surface proteins were identified in combined with various proteomic methods. Biotinylated membranous proteins in lung cancer cell lines were collected and identified by the shot-gun analysis. Expression levels of identified proteins in four different histological types of lung cancer cell line were examined by the immunoblot and immunohistochemical analyses. Serum levels of these proteins were also examined in patients with lung cancer and healthy controls by the reverse-phase protein array (RPPA) method. From identified 92 membranous proteins including CD109, CD155 and Roundabout Guidance Receptor 1 (ROBO1), we focused on the CD155 protein. Serum levels of CD155 were significantly higher in patients with adenocarcinoma and squamous cell carcinoma than in healthy controls (p < 0.0001), and the area under the curve (AUC) of receiver-operating characteristic curve (ROC) analysis was 0.87, when an optimal cut-off value of 0.31 was applied, the diagnostic sensitivity and specificity for lung cancer were 81 and 82%, respectively. To our knowledge, this is the first report providing evidence that CD155 may be a sero-diagnostic marker for non-small cell lung cancer. This methodology was shown to be useful for acquisition of novel biomarkers for membranous proteins.</p>

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