Abstract
Circulating microvesicles (cMV) are cell-derived structures that are abundantly present in the blood. Tumor cells produce large quantities of cMV, and their abundance has been shown to correlate with tumor invasiveness and resistance to therapy. This study attempts to understand the origin, composition, and potential clinical utility of cMV, analyzing their protein composition in patients with non-small cell lung cancer (NSCLC) and identifying a cMV-based biosignature that can be used to predict the presence of tumors from a blood sample.
cMV were isolated from plasma samples that were obtained from an initial cohort of 65 patients with NSCLC and from 46 control samples. A discovery panel of 63 specific biomarkers was used to develop an assay with high specificity and sensitivity based on 4 cMV surface proteins. Using a novel cMV-based multiplexed analysis platform we optimized a threshold level for 4 significant cMV subpopulations to effectively distinguish lung cancer patients from controls.
The multiplex assay included 1 general cMV marker (CD81) and 3 lung cancer-associated biomarkers: the lung epithelial C-type lectin members SPD and SPA, plus the sialoprotein osteopontin. The decision tree analysis, based on specific cut offs, showed a sensitivity of 81% and a specificity of 90%.
These results provide initial evidence that the identification of biosignatures in distinct subpopulations of cMV may offer a powerful blood-based approach for the detection and monitoring of specific disease states, such as NSCLC.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4156. doi:10.1158/1538-7445.AM2011-4156