Abstract

Abstract This study aims to identify novel biomarkers or therapeutic targets for lung cancers. We used cDNA microarrays for screening genes encoding transmembrane/secretory proteins that are up-regulated in lung cancers. During this process, we identified a secreted protein, LASEP3 (lung cancer-associated serum protein 3) as a candidate. Immunohistochemical staining of LASEP3 showed that LASEP3 expression was observed in 198 (54.8%) of 361 NSCLCs (non-small cell lung cancer) that had undergone curative surgery. High level of LASEP3 expression was associated with poor prognosis for NSCLC patients. (P=0.0183 by log-rank test). Serum LASEP3 levels were higher in NSCLC patients than in healthy volunteers. The proportion of serum LASEP3-positive cases was 160 (61.8%) of 259 NSCLCs (49.4% for stage I-II, 67.4% for stage III-IV), while 6 (5.5%) of 109 healthy volunteers were falsely diagnosed. Moreover serum LASEP3 levels were significantly higher in breast and colon cancer patients than in healthy volunteers. LASEP3 protein was overexpressed in breast and colon cancer tissues. Furthermore, reduction of LASEP3 by siRNA suppressed lung cancer cell proliferation and invasion. Flow cytometric analysis of these tumor cells transfected with siRNAs for LASEP3 revealed a significant increase of the cells at the G1 phase. Furthermore, subsequent microarray analysis of these cancer cells identified several candidate downstream genes of LASEP3 that relate to cell growth signals. These data suggest that LASEP3 is a possible diagnostic and prognostic biomarker and therapeutic target for lung and various types of solid cancer. Citation Format: Atsushi Takano, Yusuke Nakamura, Yataro Daigo. Characterization of LASEP3 as a serological and prognostic biomarker and a therapeutic target for lung cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 868. doi:10.1158/1538-7445.AM2014-868

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