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

被引:54
作者
Devriese, L. A. [1 ,2 ]
Bosma, A. J. [1 ]
van de Heuvel, M. M. [3 ]
Heemsbergen, W. [4 ]
Voest, E. E. [5 ]
Schellens, J. H. M. [1 ,2 ,6 ]
机构
[1] Netherlands Canc Inst, Div Expt Therapy, NL-1066 CX Amsterdam, Netherlands
[2] Netherlands Canc Inst, Dept Clin Pharmacol, NL-1066 CX Amsterdam, Netherlands
[3] Netherlands Canc Inst, Dept Thorac Oncol, NL-1066 CX Amsterdam, Netherlands
[4] Netherlands Canc Inst, Dept Bioinformat & Stat, NL-1066 CX Amsterdam, Netherlands
[5] Univ Med Ctr Utrecht, Dept Med Oncol, NL-3508 GA Utrecht, Netherlands
[6] Univ Utrecht, Fac Sci, Dept Pharmaceut Sci, Div Drug Toxicol, NL-3508 TB Utrecht, Netherlands
关键词
Advanced non-small cell lung cancer; Circulating tumor cell; CTC; Detection; Quantitative PCR; POLYMERASE-CHAIN-REACTION; PERIPHERAL-BLOOD; MESSENGER-RNA; PREDICT SURVIVAL; PROGRESSION-FREE; BREAST; EXPRESSION; PCR; PROSTATE; PLATFORM;
D O I
10.1016/j.lungcan.2011.07.003
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 CFCs 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. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:242 / 247
页数:6
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