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

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 pat...

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Autores principales: Zhang, Yue, Zarrabi, Kevin, Hou, Wei, Madajewicz, Stefan, Choi, Minsig, Zucker, Stanley, Chen, Wen-Tien
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6027397/
https://www.ncbi.nlm.nih.gov/pubmed/29882767
http://dx.doi.org/10.3390/biomedicines6020069
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author Zhang, Yue
Zarrabi, Kevin
Hou, Wei
Madajewicz, Stefan
Choi, Minsig
Zucker, Stanley
Chen, Wen-Tien
author_facet Zhang, Yue
Zarrabi, Kevin
Hou, Wei
Madajewicz, Stefan
Choi, Minsig
Zucker, Stanley
Chen, Wen-Tien
author_sort Zhang, Yue
collection PubMed
description 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.
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spelling pubmed-60273972018-07-13 Assessing Clinical Outcomes in Colorectal Cancer with Assays for Invasive Circulating Tumor Cells Zhang, Yue Zarrabi, Kevin Hou, Wei Madajewicz, Stefan Choi, Minsig Zucker, Stanley Chen, Wen-Tien Biomedicines Article 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. MDPI 2018-06-06 /pmc/articles/PMC6027397/ /pubmed/29882767 http://dx.doi.org/10.3390/biomedicines6020069 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zhang, Yue
Zarrabi, Kevin
Hou, Wei
Madajewicz, Stefan
Choi, Minsig
Zucker, Stanley
Chen, Wen-Tien
Assessing Clinical Outcomes in Colorectal Cancer with Assays for Invasive Circulating Tumor Cells
title Assessing Clinical Outcomes in Colorectal Cancer with Assays for Invasive Circulating Tumor Cells
title_full Assessing Clinical Outcomes in Colorectal Cancer with Assays for Invasive Circulating Tumor Cells
title_fullStr Assessing Clinical Outcomes in Colorectal Cancer with Assays for Invasive Circulating Tumor Cells
title_full_unstemmed Assessing Clinical Outcomes in Colorectal Cancer with Assays for Invasive Circulating Tumor Cells
title_short Assessing Clinical Outcomes in Colorectal Cancer with Assays for Invasive Circulating Tumor Cells
title_sort assessing clinical outcomes in colorectal cancer with assays for invasive circulating tumor cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6027397/
https://www.ncbi.nlm.nih.gov/pubmed/29882767
http://dx.doi.org/10.3390/biomedicines6020069
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