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Circulating tumor cell detection in advanced non-small cell lung cancer patients by multi-marker QPCR analysis

Abstract Background The aim of this study was to explore circulating tumor cell (CTC) detection in advanced non-small cell lung cancer (NSCLC). CTCs may not only serve as a prognostic marker in selected tumor types, but may also be useful as pharmacodynamic marker in drug development. Methods Fourty...

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Published in:Lung cancer (Amsterdam, Netherlands) Netherlands), 2012-02, Vol.75 (2), p.242-247
Main Authors: Devriese, L.A, Bosma, A.J, van de Heuvel, M.M, Heemsbergen, W, Voest, E.E, Schellens, J.H.M
Format: Article
Language:English
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Summary:Abstract Background The aim of this study was to explore circulating tumor cell (CTC) detection in advanced non-small cell lung cancer (NSCLC). CTCs may not only serve as a prognostic marker in selected tumor types, but may also be useful as pharmacodynamic marker in drug development. Methods Fourty-six advanced NSCLC patients and fourty-six healthy controls were included in the study and 8.0 ml of peripheral blood was obtained from each of the participants. Immunomagnetic bead enrichment for cells expressing epithelial cell adhesion molecule (EpCAM) was performed, followed by multi-marker quantitative real-time PCR of a panel of marker genes: cytokeratin 7 (CK7), cytokeratin 19 (CK19), human epithelial glycoprotein (EGP) and fibronectin 1 (FN1). Using quadratic discriminant analysis (QDA), expression values were combined into a single score, which indicated CTC-positivity or -negativity. Test characteristics were assessed using receiver operating characteristic (ROC) curve analysis. Results ROC curve analysis showed capability of discrimination between advanced NSCLC patients and healthy controls (area = 0.712; 95% CI 0.606–0.819; P < 0.001). A cut-off minimizing overall misclassification for QDA-positivity reached a sensitivity of 46% (95% CI 31–61) and a specificity of 93% (95% CI 82–99). Conclusions In this exploratory study, an assay was developed for discriminating CTCs in peripheral blood samples of advanced NSCLC patients from healthy controls. The assay demonstrated an acceptable sensitivity in combination with good specificity. Further validation studies should take place in NSCLC patients and a matched control group.
ISSN:0169-5002
1872-8332
DOI:10.1016/j.lungcan.2011.07.003