Abstract 3920: Identification of LASEP1 as a new serological and prognostic biomarker and a therapeutic target for lung cancer

Abstract

Abstract Lung cancer is the leading cause of cancer deaths in the world and the overall prognosis remains poor. The poor prognosis of lung cancer patients is largely a result of the occult metastatic dissemination. Thus, the development of early cancer detection biomarker and new treatment is required. 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. As a result of this process, we identified a secreted protein, LASEP1 (lung cancer-associated serum protein 1) as a candidate. Immunohistochemical staining of LASEP1 showed that LASEP1 expression was observed in 210 (56.1%) of 374 NSCLC (non-small cell lung cancer) that had undergone curative surgery. High level of LASEP1 expression was associated with poor prognosis for NSCLC patients (P<0.0001 by log-rank test). Serum LASEP1 levels were higher in NSCLC patients than in healthy volunteers. The proportion of serum LASEP1-positive cases was 127 (38.6%) of 329 NSCLCs, while 4 (3.9%) of 102 healthy volunteers were falsely diagnosed. Furthermore, reduction of LASEP1 by siRNA significantly induced the apoptosis of lung cancer cells. Furthermore, the growth activity of the LASEP1-positive cells was neutralized by addition of originally developed anti-LASEP1 monoclonal antibodies into their culture media, and the systemic administration of the anti-LASEP1 antibody to tumor-implanted mice significantly suppressed tumor growth without any adverse events. By gene expression analysis using microarray and mRNAs from lung cancer cells transfected with siRNA for LASEP1, we identified WHSC1 gene that encodes an oncogenic histone methyltransferase as one of LASEP1-target genes. These data suggest that LASEP1 is a possible diagnostic and prognostic biomarker and therapeutic target for lung cancer. Citation Format: Atsushi Takano, Yusuke Nakamura, Yataro Daigo. Identification of LASEP1 as a new serological and prognostic biomarker and a therapeutic target for lung cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3920. doi:10.1158/1538-7445.AM2015-3920