title: S100A16 is a Prognostic Marker for Lung Adenocarcinomas.
abstract: BACKGROUND
  Many functional molecules controlling diverse cellular function are included in low-molecular weight proteins and peptides.
  
  
  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.
authors.affiliation: Department of Applied Tumor Pathology, Graduate School of Medical Sciences, Kitasato University, Kanagawa, Japan E-mail : yuichi@med.kitasato-u.ac.jp.
authors.forename: Keita
authors.initials: K
authors.lastname: Saito
authors.forename: Makoto
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Ryo
authors.initials: R
authors.lastname: Nagashio
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Ryuge
authors.forename: Ken
authors.initials: K
authors.lastname: Katono
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Nakashima
authors.forename: Benio
authors.initials: B
authors.lastname: Tsuchiya
authors.forename: Shi-Xu
authors.initials: SX
authors.lastname: Jiang
authors.forename: Makoto
authors.initials: M
authors.lastname: Saegusa
authors.forename: Yukitoshi
authors.initials: Y
authors.lastname: Satoh
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Masuda
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Sato
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry* / Q000378:metabolism / Q000473:pathology*; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D001808:Blood Vessels / Q000473:pathology; D018278:Carcinoma, Neuroendocrine / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000737:chemistry*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000737:chemistry* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010994:Pleura / Q000473:pathology; D011379:Prognosis; D009418:S100 Proteins / Q000032:analysis* / Q000378:metabolism; D012737:Sex Factors; D055752:Small Cell Lung Carcinoma / Q000378:metabolism; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D009418:S100 Proteins; C000589580:S100A16 protein, human