Background: Many functional molecules controlling diverse cellular function are included in low-molecularweight proteins and peptides. Materials and Methods: To identify proteins controlling function in lungadenocarcinomas (AC), we performed two-dimensional gel electrophoresis employing tricine-SDS polyacrylamidein the second dimension (tricine 2-DE). This system was able to detect proteins under 1 kDa even with posttranslationalmodifications. To confirm the utility of detected proteins as novel tumor markers for AC, weperformed 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 cellscompared with lung squamous cell carcinoma, small cell carcinoma, and large cell neuroendocrine carcinomaderivedcells. Immunohistochemically, S100A16 showed various subcellular localization in lung cancer tissuesand 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, membranousstaining of S100A16 was significantly correlated with a poorer overall survival of either stage I (P=0.0088) orstage II / III (P=0.0003) lung AC patients, and multivariate analysis confirmed that membranous expression ofS100A16 was an independent adverse prognostic indicator (P=0.0001). Conclusions: The present results suggestthat S100A16 protein is a novel prognostic marker for lung AC.
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