Identification of LASEP3 as a new serological and prognostic biomarker for lung and various type of cancer.

Abstract

e13565 Background: Identification of early cancer detection and prognostic biomarkers is urgently required to improve clinical outcome. Methods: We have screened cancer biomarkers using a strategy as follows; i)To identify up-regulated genes in non-small cell lung cancers (NSCLCs) using the cDNA microarray representing 27,648 genes and 120 lung cancers, ii) To verify the candidate genes for their no or low expression in 23 normal tissues by northern-blot analysis, iii)To validate clinicopathological significance of their protein expression by tissue microarray consisting of 259 lung cancers, iv) To verify whether they are essential for the growth of cancer cells by siRNA assay, and v) To measure their serum protein levels by ELISA in patients with various type of cancers. Results: We identified LASEP3 (Lung cancer Associated Serum Protein 3) encoding secreted protein as a candidate. Immunohistochemical analysis showed that LASEP3 was frequently over-expressed in various histological types of lung cancers; positive staining of LASEP3 was observed in 198 (54.8%) of 361 NSCLCs. In addition, a high level of LASEP3 expression was associated with poor prognosis of patients with NSCLC (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; 131 (63.6%) of 206 ADCs and 29 (54.7%) of 53 SCCs, while 6 (5.5%) of 109 healthy volunteers were falsely diagnosed. Serum LASEP3 levels were significantly higher in breast and colon cancer patients than in healthy volunteers, and tissue LASEP3 protein was overexpressed in breast and colon cancer tissues. Furthermore, treatment of lung cancer cells with siRNAs against LASEP3 suppressed its expression and resulted in growth suppression of cancer cells. Induction of exogenous expression of LASEP3 promoted cell mobility in vitro. We found a 50-kDa receptor (LASEPR) which interacts with LASEP3 on cancer cell surface, suggesting that LASEP3 is an autocrine/paracrine growth factor. Conclusions: LASEP3 is a potential target for the development of diagnostic and prognostic biomarkers for lung and various types of cancers