Abstract 4829: Evaluation prognostic significance of circulating tumor cells (CTCs) using multiplexed gold nanoparticles in patients with head and neck cancer
Authors: Wang Xu , Qian Ximei , Beitler Jonathan J. , Zhang Jun , Kang Hyunseok , Chen Zhuo (Georgia) , Magliocca Kelly R. , Wang Xiaojing , Chen Zhengjia , Nie Shuming , Shin Dong M. 
Published: May 2015

Abstract
Background: Detection, quantification, and molecular characterization of CTCs may aid physicians in optimizing treatment. However, current approaches for CTC detection, including CellSearch (FDA approved CTC detection method) rely on a single biomarker, whic may not be appropriate for heterogeneous tumors.
Methods: We developeda multiplexed single-tube assay using two targeting Surface-Enhanced Raman scattering (SERS) nanoparticles for directdetection of CTCs in blood sample. The two SERS nanoparticles were distinguished with unique spectral signatures were targeted for simultaneous detection of the biomarkers epidermal growth factor receptor (EGFR) and epithelial cell adhesion molecule (EpCAM). The correlation of CTC level detected by two biomarkers with clinical characteristics was evaluated and compared.
Results: CTCs were present in 60.9% of patients (39 of 64 patients) with a range of 5-1751 cells per ml of whole blood. CTC levels detected by EGFR-tag (CTC-EGFR) and EpCAM-tag (CTC-EpCAM) were strongly cross-correlated (P&lt;0.001). CTC levels detected by both biomarkers correlated significantly with the presence of disease (P=0.005 and P&lt;0.0001 for CTC-EGFR and CTC-EpCAM, respectively). In univariate analysis, CTC level detected by both biomarkers associated significantly with disease free survival (hazard ratio: 2.135; 95%CI: 1.028 to 4.435; P=0.042 for CTC-EGFR, and hazard ratio: 6.028; 95%CI: 2.294 to 12.84; P=0.0003 for CTC-EpCAM). In multivariate analysis, CTC level detected by EpCAM-tag but not by EGFR-tag was significant prognostic factor for disease free survival (hazard ratio: 6.771; 95%CI: 2.069 to 22.151; P=0.0016). Thus, the CTC level detected by EpCAM-tag has stronger association with disease free survival than that by EGFR-tag.
Conclusions: We have developed two SERS nanoparticles, allowed the simultaneous detection of EGFR or EpCAM on CTCs from one blood sample. CTC levels detected by both biomarkers associated significantly with disease statue and disease free survival. CTC level detected by EpCAM-tag but not by EGFR-tag was significant prognostic factor for disease free survival. Our technique based on two biomarkers, compared with those relying on a single biomarker, may improve CTC assessment in clinical settings. (This research was supported by the National Cancer Institute awards 5 P50 CA128613 and U54CA119338-04).
Citation Format: Xu Wang, Ximei Qian, Jonathan J. Beitler, Jun Zhang, Hyunseok Kang, Zhuo (Georgia) Chen, Kelly R. Magliocca, Xiaojing Wang, Zhengjia Chen, Shuming Nie, Dong M. Shin. Evaluation prognostic significance of circulating tumor cells (CTCs) using multiplexed gold nanoparticles in patients with head and neck cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4829. doi:10.1158/1538-7445.AM2014-4829