178P - Tumor Endothelial Markers (TEMS) as Prognostic and Predictive Markers in Non-Small Cell Lung Cancer (NSCLC)

Abstract

ABSTRACT Background Tumor angiogenesis plays a crucial role in tumor development and progression. Genome analyses of endothelial cells identified genes specifically expressed by tumor endothelial cells. These so called tumor endothelial markers (TEMs) are discussed as potential new therapeutic targets or as biomarkers for monitoring anti-angiogenic therapies. In non-small cell lung cancer (NSCLC) the role of TEMs is not yet investigated. Therefore, the present study aims to define the expression of TEMs in NSCLC cancer cell lines and tumor samples of NSCLC patients. Patients and methods The expression of different TEMs (Robo4, Clec14 and ECSCR) was evaluated by qPCR and Western blot analyses in several NSCLC cancer cell lines (A549, Calu1, Colo699) compared to human umbilical vein endothelial cells (HUVEC) and human bronchial epithelial cells (HBEpC). The expression of TEMs in resected tumor tissue of NSCLC patients (n = 64) was measured by qPCR and compared to adjacent lung tissue (n = 52). Further correlation analyses of patient samples with clinical course were performed using the data from the TYROL register. Results NSCLC cancer cell lines and HBEpC do not express TEMs neither on mRNA or on protein level compared to HUVECs (p = 0.001). Quantitative analyses of Robo4, ECSCR and Clec14 mRNA expression showed a significant up-regulation of CLEC14 in tumor samples (p = 0.01). Evaluating paired tissue samples from cancerous and corresponding non-cancerous tissues (n = 31) also Robo4 showed a significant upregulation in cancer specimens (p = 0.04). ECSCR showed a statistical trend towards an overexpression in tumor tissue (p = 0.09). Immunohistochemichal analyses of Robo4 revealed a higher expression in tumor tissue in comparison to the adjacent tissue (tumor vs. adjacent tissue; n = 20). Correlation with clinical data showed that increased TEM expression correlated with prolonged overall survival of NSCLC patients. Conclusion TEMs are overexpressed in NSCLC tissue specimens but not in cancer cells suggesting that TEMs are upregulated in stromal tissue including tumor vessels. Therefore, TEMs provide a potential new target structure for anti-angiogenic therapies. Increased TEM expression levels correlated with prolonged OS possibly due to vascular stabilization. Disclosure All authors have declared no conflicts of interest.