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Assessing Clinical Outcomes in Colorectal Cancer with Assays for Invasive Circulating Tumor Cells

Stony Brook Medicine, Stony Brook, NY 11794, USA
Division of Hematology/Oncology, Department of Medicine, Stony Brook University Hospital, Stony Brook, NY 11794, USA
Department of Medicine and Research, Veterans Affairs Medical Center, Northport, NY 11768, USA
Vitatex Inc., 25 Health Sciences Drive, Stony Brook, NY 11790, USA
Author to whom correspondence should be addressed.
Biomedicines 2018, 6(2), 69;
Received: 10 April 2018 / Revised: 17 May 2018 / Accepted: 1 June 2018 / Published: 6 June 2018
(This article belongs to the Special Issue Cancer Biomarkers and Targets in Digestive Organs)
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Colorectal carcinoma (CRC) is the second leading cause of cancer-related mortality. The goals of this study are to evaluate the association between levels of invasive circulating tumor cells (iCTCs) with CRC outcomes and to explore the molecular characteristics of iCTCs. Peripheral blood from 93 patients with Stage I–IV CRC was obtained and assessed for the detection and characterization of iCTCs using a functional collagen-based adhesion matrix (CAM) invasion assay. Patients were followed and assessed for overall survival. Tumor cells isolated by CAM were characterized using cell culture and microarray analyses. Of 93 patients, 88 (95%) had detectable iCTCs, ranging over 0–470 iCTCs/mL. Patients with Stage I–IV disease exhibited median counts of 0.0 iCTCs/mL (n = 6), 13.0 iCTCs/mL (n = 12), 41.0 iCTCs/mL (n = 12), and 133.0 iCTCs/mL (n = 58), respectively (p < 0.001). Kaplan–Meier curve analysis demonstrated a significant survival benefit in patients with low iCTC counts compared with in patients with high iCTC counts (log-rank p < 0.001). Multivariable Cox model analysis revealed that iCTC count was an independent prognostic factor of overall survival (p = 0.009). Disease stage (p = 0.01, hazard ratio 1.66; 95% confidence interval: 1.12–2.47) and surgical intervention (p = 0.03, HR 0.37; 95% CI: 0.15–0.92) were also independent prognostic factors. Gene expression analysis demonstrated the expression of both endothelial and tumor progenitor cell biomarkers in iCTCs. CAM-based invasion assay shows a high detection sensitivity of iCTCs that inversely correlated with overall survival in CRC patients. Functional and gene expression analyses showed the phenotypic mosaics of iCTCs, mimicking the survival capability of circulating endothelial cells in the blood stream. View Full-Text
Keywords: circulating tumor cells; colorectal carcinoma; CAM invasion assay; phenotypic mosaics; tumor progenitor circulating tumor cells; colorectal carcinoma; CAM invasion assay; phenotypic mosaics; tumor progenitor

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Zhang, Y.; Zarrabi, K.; Hou, W.; Madajewicz, S.; Choi, M.; Zucker, S.; Chen, W.-T. Assessing Clinical Outcomes in Colorectal Cancer with Assays for Invasive Circulating Tumor Cells. Biomedicines 2018, 6, 69.

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