O2–032 - Characterization of a Lung Cancer Growth Factor, LASEP3 as a Serological and Prognostic Biomarker and Therapeutic Target

Abstract

Identification of early cancer detection and prognostic biomarkers is urgently required to improve clinical outcome. To identify novel biomarkers or therapeutic targets for lung cancers, we have been screening genes encoding transmembrane/secretory proteins that are up-regulated in lung cancers, using the cDNA microarray representing 27,648 genes and 120 lung cancers. During this process, we identified a secreted protein, LASEP3 (lung cancer-associated serum protein 3) as a candidate. Immunohistochemical analysis showed that strong positive staining of LASEP3 was observed in 198 (54.8%) of 361 NSCLCs (non-small cell lung cancer). High level of LASEP3 expression was associated with poor prognosis of NSCLCpatients. (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, 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. 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. In addition, the use of both LASEP3 and proGRP increased sensitivity because 78.3% of the lung SCLC patients were diagnosed as positive, whereas only 6.6% of 121 healthy volunteers were falsely diagnosed. LASEP3 protein was overexpressed in breast, cervical and colon cancer tissues. Furthermore, treatment of lung cancer cells with LASEP3-siRNAs suppressed its expression and suppressed cell growth and invasion. To clarify the mechanism of tumor suppression by siRNAs against LASEP3, we performed flow cytometric analysis of the tumor cells transfected with these siRNAs. We found a significant increase of the cells at the G0/G1 phase. These data suggest that LASEP3 is a diagnostic and prognostic biomarker and therapeutic target for lung and various type of human cancer. Identification of early cancer detection and prognostic biomarkers is urgently required to improve clinical outcome. To identify novel biomarkers or therapeutic targets for lung cancers, we have been screening genes encoding transmembrane/secretory proteins that are up-regulated in lung cancers, using the cDNA microarray representing 27,648 genes and 120 lung cancers. During this process, we identified a secreted protein, LASEP3 (lung cancer-associated serum protein 3) as a candidate. Immunohistochemical analysis showed that strong positive staining of LASEP3 was observed in 198 (54.8%) of 361 NSCLCs (non-small cell lung cancer). High level of LASEP3 expression was associated with poor prognosis of NSCLCpatients. (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, 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. 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. In addition, the use of both LASEP3 and proGRP increased sensitivity because 78.3% of the lung SCLC patients were diagnosed as positive, whereas only 6.6% of 121 healthy volunteers were falsely diagnosed. LASEP3 protein was overexpressed in breast, cervical and colon cancer tissues. Furthermore, treatment of lung cancer cells with LASEP3-siRNAs suppressed its expression and suppressed cell growth and invasion. To clarify the mechanism of tumor suppression by siRNAs against LASEP3, we performed flow cytometric analysis of the tumor cells transfected with these siRNAs. We found a significant increase of the cells at the G0/G1 phase. These data suggest that LASEP3 is a diagnostic and prognostic biomarker and therapeutic target for lung and various type of human cancer.