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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2018
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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. |
format | Online Article Text |
id | pubmed-6027397 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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