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

Abstract

10552 Background: Characterization of cancer-specific oncoantigens is an effective strategy to identify novel diagnostic/prognostic biomarkers. Methods: We screened for genes encoding transmembrane/secretory molecules that are transactivated commonly in lung cancers by the gene-expression profile analysis of 120 lung cancers. LASEP3 (lung cancer-associated serum protein 3) that encodes a secretory protein was selected as a candidate. Immunohistochemical staining using lung cancer tissue microarray was applied to examine the expression level of LASEP3 and its prognostic value. Serum LASEP3 levels in lung cancer patients and healthy individuals were measured by ELISA. A role of LASEP3 in cancer cell growth was examined by small interfering RNA experiments. Results: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 for NSCLC patients (P=0.0183) and a high level of LASEP3 expression was associated with tumor size (P = 0.0183) and lymph node metastasis (P = 0.0016). 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. A combined assay using both LASEP3 and CEA increased sensitivity because 79.5% of the NSCLC patients were then diagnosed as positive, whereas only 7.3% of 109 healthy volunteers were falsely diagnosed as positive. Serum LASEP3 levels were significantly higher in other types of cancer (breast, cervical, and colon cancer) patients than in healthy volunteers. Furthermore, treatment of lung cancer cells with siRNAs against LASEP3 suppressed its expression and resulted in growth suppression of the lung cancer cells. Conclusions: We have identified LASEP3 as a potential target for the development of diagnostic and prognostic biomarkers for lung cancer.