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S100A16 is a Prognostic Marker for Lung Adenocarcinomas

  • Saito, Keita (Department of Applied Tumor Pathology, Graduate School of Medical Sciences, Kitasato University) ;
  • Kobayashi, Makoto (Department of Applied Tumor Pathology, Graduate School of Medical Sciences, Kitasato University) ;
  • Nagashio, Ryo (Department of Applied Tumor Pathology, Graduate School of Medical Sciences, Kitasato University) ;
  • Ryuge, Shinichiro (Department of Respiratory Medicine, Kitasato University) ;
  • Katono, Ken (Department of Respiratory Medicine, Kitasato University) ;
  • Nakashima, Hiroyasu (Department of Thoracic and Cardiovascular Surgery, Kitasato University) ;
  • Tsuchiya, Benio (Department of Applied Tumor Pathology, Graduate School of Medical Sciences, Kitasato University) ;
  • Jiang, Shi-Xu (Department of Pathology, School of Medicine, Kitasato University) ;
  • Saegusa, Makoto (Department of Pathology, School of Medicine, Kitasato University) ;
  • Satoh, Yukitoshi (Department of Thoracic and Cardiovascular Surgery, Kitasato University) ;
  • Masuda, Noriyuki (Department of Respiratory Medicine, Kitasato University) ;
  • Sato, Yuichi (Department of Applied Tumor Pathology, Graduate School of Medical Sciences, Kitasato University)
  • Published : 2015.11.04

Abstract

Background: Many functional molecules controlling diverse cellular function are included in low-molecular weight proteins and peptides. Materials and Methods: To identify proteins controlling function in lung adenocarcinomas (AC), we performed two-dimensional gel electrophoresis employing tricine-SDS polyacrylamide in the second dimension (tricine 2-DE). This system was able to detect proteins under 1 kDa even with post-translational modifications. To confirm the utility of detected proteins as novel tumor markers for AC, we performed immunohistochemical analysis using 170 formalin-fixed and paraffin-embedded lung AC tissues. Results: Tricine 2-DE revealed that five proteins including S100A16 were overexpressed in lung AC-derived cells compared with lung squamous cell carcinoma, small cell carcinoma, and large cell neuroendocrine carcinoma-derived cells. Immunohistochemically, S100A16 showed various subcellular localization in lung cancer tissues and a membranous staining status was correlated with the T-factor (P=0.0008), pathological stage (P=0.0015), differentiation extent (P=0.0001), lymphatic invasion (P=0.0007), vascular invasion (P=0.0001), pleural invasion (P=0.0087), and gender (P=0.039), but not with the age or smoking history. More importantly, membranous staining of S100A16 was significantly correlated with a poorer overall survival of either stage I (P=0.0088) or stage II / III (P=0.0003) lung AC patients, and multivariate analysis confirmed that membranous expression of S100A16 was an independent adverse prognostic indicator (P=0.0001). Conclusions: The present results suggest that S100A16 protein is a novel prognostic marker for lung AC.

Keywords

Lung cancer;adenocarcinoma;S100A16;tricine-2DE;tumor marker

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