Abstract 2724: Human lipoproteins, a new serum compartment for tracking biomarkers: an illustrative study of soluble VE-cadherin in malignant gliomas

• Published in: Cancer research (Chicago, Ill.) Ill.), 2010-04, Vol.70 (8_Supplement), p.2724-2724
• Main Authors: Cand, Francine, Pelletier, Laurent, Mannic, Tiphaine, Boccard, Sandra, Laporte, François, Laffont, Jean-Luc, Gauchez, Anne-Sophie, Gulino-Debrac, Daniele, Huber, Phillipe, Berger, François, Vilgrain, Isabelle
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM10-2724

BACKGROUND: Vascular endothelial (VE)-cadherin is an endothelial specific adhesion molecule of vital importance for the maintenance of endothelium integrity. Because gliomas are hypervascular tumors, the present study was designed to address the question whether Vascular endothelial-cadherin (VE-cadherin), a protein exclusively expressed in endothelial cells, could be a potential candidate biomarker for clinical use in the setting of gliomas. METHODS: Fifty-six patients newly diagnosed glioma who underwent radiochemotherapy were enrolled in this retrospective study. Serum samples were collected prior treatment. Therapeutic response to Temodal was observed by RMI in 24 patients (25 oligodendroglioma, 2 glioblastoma multiform) median age 42.15 (range 23-65) while 32 patients were resistant (5 anaplastic oligodendroglioma, 9 anaplastic astrocytomas and 17 glioblastomas multiforme), median age 51.9 (range 19-84). sVE-cadherin levels was evaluated by westernblotting and sandwich ELISA. Data were analyzed using logistic regression and receiver operating characteristics (ROC) curve analysis. RESULTS: VE-cadherin 90 kDa extracellular domain was detected in human serum by western blot and its accurate detection was dependent upon a pre-dilution in a detergent-containing buffer (Triton X-100). Of importance, we found that sVE-cadherin was carried by human lipoproteins and that the detergent allowed to separate both entities to increase protein detectability. Interestingly, we found that sVE cadherin was significantly lower in the non responders group as compared to responders. We developped an ELISA that clearly discriminate patients NR (0.669+/-0.104 AU) from patients R (0.975+/-0.098 AU (p=0.0024). Receiver-operating characteristic (ROC) curve analysis revealed that the predictive cut-off value of serum VE-cadherin for chemoresistance was 0.735 AU (area-under-the-curve 0.82; 95% confidence interval 0.71-0.87; maximal accuracy 0.875) Patients lipid profile (total cholesterol, triglycerides, LDL and HDL) were not significantly different between the two groups and could not account for the differences observed in serum VE-cadherin levels. CONCLUSIONS: We show for the first time that the lipoprotein component of serum — which is most often ignored in protein diagnostics — contains proteins that can unexpectedly serve as biomarkers for disease. This finding may open completely new avenues of biomarker research. Second, we demonstrate, one candidate marker (soluble VE-c