CHARACTERIZATION OF A LUNG CANCER GROWTH FACTOR, LASEP1 AS A SEROLOGICAL AND PROGNOSTIC BIOMARKER AND A THERAPEUTIC TARGET

    loading  Checking for direct PDF access through Ovid

Abstract

Identification of early cancer detection and prognostic biomarkers is urgently required to improve the clinical outcome. We have screened cancer biomarkers using a strategy as follows: (a) to identify up-regulated genes in non-small-cell lung cancers (NSCLCs) using the cDNA microarray representing 27, 648 genes and 120 lung cancers, (b) to verify the candidate genes for their no or low expression in 23 normal tissues by northern blot analysis, (c) to validate clinicopathological significance of their protein expression by using NSCLCs tissue microarray, (d) to verify whether they are essential for the growth of cancer cells by siRNA assay, and (e) to measure their serum protein levels by ELISA. We identified a secreted protein, LASEP1 (lung cancer-associated serum protein 1) as a candidate. Immunohistochemical analysis showed LASEP1 protein was frequently over-expressed in lung cancers; positive staining of LASEP1 was observed in 210 (56.1%) of 374 NSCLC. Strong LASEP1 positivity was associated with poor prognosis for patients with NSCLC (P < 0.001 by log-rank test). Serum LASEP1 levels were higher in NSCLCs patients than in healthy volunteers. The proportion of serum LASEP1-positive cases was 127 (38.6%) of 329 lung cancers. Furthermore, siRNA-mediated silencing of LASEP1 suppressed the growth of cancer cells; on the other hand, induction of exogenous expression of LASEP1 enhanced the cell growth and mobility in vitro. The growth activity of the LASEP1-positive cells was neutralized by the addition of originally developed anti-LASEP1 monoclonal antibodies into their culture media. The systemic administration of anti-LASEP1 antibody to tumor-implanted mice significantly suppressed tumor growth without any adverse events. Using GeneChip and lung cancer cells transfected with siRNAs for LASEP1, we identified several down-stream genes of LASEP1 that were related to carcinogenesis. LASEP1 is a potential target for the development of diagnostic and prognostic biomarkers for lung cancer.

Related Topics

    loading  Loading Related Articles