Correlation of pre-treatment serum levels of Magic Roundabout protein with overall survival in patients with advanced non-small cell lung cancer (NSCLC)

Abstract

7199 Background: Magic Roundabout (MR; ROBO 4) is a recently discovered gene which encodes for a protein that possess structural homology with the roundabout family of proteins. Genes of the roundabout family code for neuronal specific cell surface receptors that are involved in axon guidance. MR in contrast showed endothelial specificity in vitro and in vivo using immunohistochemistry and in situ hybridisation. The putative role of MR as an endothelial analogue of Roundabout in angiogenesis makes it a potentially attractive target for antiangiogenic cancer therapy. Patients and Methods: 20 ml venous blood was taken before chemotherapy from 193 non-fasting patients with NSCLC. These patients comprised a non-selected subset of 300 patients who were treated in a randomised phase III trial comparing gemcitabine plus vinorelbine (GV) versus gemcitabine plus vinorelbine plus cisplatin (GVP). Patients with cytologically or histologically confirmed NSCLC stage IIIB disease with malignant pleural effusion or stage IV disease were enrolled. Using specific antibodies against MR peptides we screened the pre-treatment sera of these patients for MR-protein levels. Results: The log rank test showed no statistically significant difference between both chemotherapy treatment arms (JCO, 2004) in overall survival (P = 0.79). Equally, no significant difference in overall survival could be attributed to gender (P = 0.54), stage (P = 0.92), histologic subtype (P = 0.28) or histologic grade (P = 0.87). However, patients with pre-treatment serum levels of MR-protein lower than median (E450nm =0.652) had a median overall survival of 41.0 weeks whereas those with a higher serum level had a considerably shorter median survival of 32.4 weeks. This difference in overall survival was of borderline significance (P = 0.05) in the log rank test. Conclusions: This is the first study to present clinical data that link MR serum levels with outcome in patients with NSCLC. Whether the correlation of pre-treatment serum levels of MR and survival can be attributed to MR dependent angiogenesis remains to be investigated. No significant financial relationships to disclose.