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R. Catarino

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    P1.06 - Poster Session 1 - Prognostic and Predictive Biomarkers (ID 161)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P1.06-037 - Angiopoietin-2 serum and mRNA levels as prognostic factors in Non Small Cell Lung cancer (ID 2476)

      09:30 - 16:30  |  Author(s): R. Catarino

      • Abstract

      Tumor vasculature is a very important target for the management of NSCLC, with antiangiogenic therapy becoming part of standard antitumor treatment. Angiopoietin-2 (ANG-2) is a functional ligand of the Tie2 tyrosine kinase receptor expressed on endothelial cells. The dominant biologic role of ANG-2 as a destabilizing agent of established blood vessels as a prerequisite to sprouting angiogenesis includes it among the most intensely explored target molecules for the development of second-generation antiangiogenic drugs. The aim of this study was to evaluate peripheral blood leukocytes’ ANG-2 mRNA expression levels and serum circulating levels of ANG-2 as prognostic factors for NSCLC patients.

      The study included 150 Caucasian NSCLC patients from the North region of Portugal, with a mean age of 64.0 years. The samples were collected at the time of diagnosis, before treatment, and included 52 epidermoid, 76 adenocarcinomas, 20 undifferentiated NSCLC, 2 large cells and 2 mixed carcinomas, of which 76% were male and 73,5% smokers or former smokers, divided in 77 non-metastatic and 73 metastatic cases. ANG-2 circulating levels were evaluated in subject samples with R&D Quantikine ELISA Kit, and mRNA expression levels (92 patients) with High Capacity RNA-to_cDNA[™] kit and Taqman[®]Gene Expression Assay, by real-timePCR, both from Applied Biosystems, according to manufacturer’s instructions.

      Our results demonstrate that patients with high ANG-2 circulating levels present a worst overall survival (OS) than patients with lower circulating levels (21.0 months vs 42.6 months, respectively; Log Rank Test, p=0.001). Equally, patients with high mRNA expression levels have diminished overall survival when compared to those with low mRNA expression (20.3 months vs 34.3 months, respectively; Log Rank Test, p=0.016). Moreover, Cox Regression analysis adjusted to tumor stage, smoking status and histological type indicates that both high ANG-2 circulating levels and high mRNA expression levels are independent prognostic factors in NSCLC (HR=1.83, CI95%=1.19-2.80, p=0.006; HR=1.82, CI95%=1.02-3.23, p=0.043, respectively).

      ANG-2 is considered as a major player of the angiogenic switch in the course of tumor progression, and it is found to be particularly increased in highly vascularized tumors. In fact, in some tumor models, the mRNA induction of ANG-2 in tumor endothelium has made it a very attractive circulating biomarker of angiogenesis activation. Several studies are currently investigating the promising role of ANG-2 as a target of antiangiogenic inhibitors in several cancers, as an alternative to acquired resistance to currently used anti-VEGF molecules. Our results indicate that higher levels of ANG-2 mRNA in peripheral blood leukocytes and circulating ANG-2 are associated with worst survival in NSCLC patients. Assuming that blockage of ANG-2 is achieved in tumor stroma in a near future, this might represent a new breakthrough in cancer treatment and its circulating levels and mRNA expression levels may be helpful as predictive factors of treatment response, surpassing the need to obtain tumor tissue samples to assess its levels of expression.