Circulating tumor cell levels are elevated in colorectal cancer patients with high tumor burden in the liver

Jussuf T. Kaifi, Miriam Kunkel, David T. Dicker, Jamal Joude, Joshua E. Allen, Avisnata Das, Junjia Zhu, Zhaohai Yang, Nabeel Sarwani, Guangfu Li, Kevin F. Staveley-O’Carroll, Wafik S. El-Deiry

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Background: Metastatic spread is the most common cause of cancer-related death in colorectal cancer (CRC) patients, with the liver being the mostly affected organ. Circulating tumor cells (CTCs) are a prognostic marker in stage IV CRC. We hypothesized that tumor burden in the liver correlates with CTC quantity. Methods: Blood (7.5 ml) was prospectively collected from 24 patients with novel stage IV CRC diagnosis. Baseline EpCAM+ CTCs were analyzed with the FDA-approved CellSearch® system. Clinicopathological data were collected, and hepatic tumor burden was determined by radiographic liver volumetry with contrast-enhanced CT scans. CRC primary tumors were immunohistochemically stained for EpCAM expression with BerEP4 monoclonal antibody. Statistical analyses were performed using 2-sample T-test, non-parametric Wilcoxon Rank-Sum test, and Fisher's exact test. Results: CTCs were detected n 17 (71%) of 24 patients. The overall mean CTC number as determined by EpCAM-based CellSearch® detection was 6.3 (SEM 2.9). High baseline CTC numbers (≥3) correlated significantly with a high tumor/liver ratio (≥30%), and with high serum CEA levels, as determined by two-sample T-test on log-transformed data and by Fisher's Exact test on categorical data analysis (P < 0.05). The CRC primary tumors were consistently expressing EpCAM by immunostaining. Conclusions: High tumor burden in the liver and high baseline serum CEA levels are associated with high number of baseline CTCs in stage IV CRC patients. Future studies should further investigate the biological role and expression patterns of single CTCs in cancer patients to further improve personalized treatment strategies.

Original languageEnglish (US)
Pages (from-to)690-698
Number of pages9
JournalCancer Biology and Therapy
Volume16
Issue number5
DOIs
StatePublished - Jan 1 2015

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Circulating Neoplastic Cells
Tumor Burden
Colorectal Neoplasms
Liver
Neoplasms
Nonparametric Statistics
Cell Count
Serum
Monoclonal Antibodies
Epithelial Cell Adhesion Molecule

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research

Cite this

Kaifi, J. T., Kunkel, M., Dicker, D. T., Joude, J., Allen, J. E., Das, A., ... El-Deiry, W. S. (2015). Circulating tumor cell levels are elevated in colorectal cancer patients with high tumor burden in the liver. Cancer Biology and Therapy, 16(5), 690-698. https://doi.org/10.1080/15384047.2015.1026508
Kaifi, Jussuf T. ; Kunkel, Miriam ; Dicker, David T. ; Joude, Jamal ; Allen, Joshua E. ; Das, Avisnata ; Zhu, Junjia ; Yang, Zhaohai ; Sarwani, Nabeel ; Li, Guangfu ; Staveley-O’Carroll, Kevin F. ; El-Deiry, Wafik S. / Circulating tumor cell levels are elevated in colorectal cancer patients with high tumor burden in the liver. In: Cancer Biology and Therapy. 2015 ; Vol. 16, No. 5. pp. 690-698.
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title = "Circulating tumor cell levels are elevated in colorectal cancer patients with high tumor burden in the liver",
abstract = "Background: Metastatic spread is the most common cause of cancer-related death in colorectal cancer (CRC) patients, with the liver being the mostly affected organ. Circulating tumor cells (CTCs) are a prognostic marker in stage IV CRC. We hypothesized that tumor burden in the liver correlates with CTC quantity. Methods: Blood (7.5 ml) was prospectively collected from 24 patients with novel stage IV CRC diagnosis. Baseline EpCAM+ CTCs were analyzed with the FDA-approved CellSearch{\circledR} system. Clinicopathological data were collected, and hepatic tumor burden was determined by radiographic liver volumetry with contrast-enhanced CT scans. CRC primary tumors were immunohistochemically stained for EpCAM expression with BerEP4 monoclonal antibody. Statistical analyses were performed using 2-sample T-test, non-parametric Wilcoxon Rank-Sum test, and Fisher's exact test. Results: CTCs were detected n 17 (71{\%}) of 24 patients. The overall mean CTC number as determined by EpCAM-based CellSearch{\circledR} detection was 6.3 (SEM 2.9). High baseline CTC numbers (≥3) correlated significantly with a high tumor/liver ratio (≥30{\%}), and with high serum CEA levels, as determined by two-sample T-test on log-transformed data and by Fisher's Exact test on categorical data analysis (P < 0.05). The CRC primary tumors were consistently expressing EpCAM by immunostaining. Conclusions: High tumor burden in the liver and high baseline serum CEA levels are associated with high number of baseline CTCs in stage IV CRC patients. Future studies should further investigate the biological role and expression patterns of single CTCs in cancer patients to further improve personalized treatment strategies.",
author = "Kaifi, {Jussuf T.} and Miriam Kunkel and Dicker, {David T.} and Jamal Joude and Allen, {Joshua E.} and Avisnata Das and Junjia Zhu and Zhaohai Yang and Nabeel Sarwani and Guangfu Li and Staveley-O’Carroll, {Kevin F.} and El-Deiry, {Wafik S.}",
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Kaifi, JT, Kunkel, M, Dicker, DT, Joude, J, Allen, JE, Das, A, Zhu, J, Yang, Z, Sarwani, N, Li, G, Staveley-O’Carroll, KF & El-Deiry, WS 2015, 'Circulating tumor cell levels are elevated in colorectal cancer patients with high tumor burden in the liver', Cancer Biology and Therapy, vol. 16, no. 5, pp. 690-698. https://doi.org/10.1080/15384047.2015.1026508

Circulating tumor cell levels are elevated in colorectal cancer patients with high tumor burden in the liver. / Kaifi, Jussuf T.; Kunkel, Miriam; Dicker, David T.; Joude, Jamal; Allen, Joshua E.; Das, Avisnata; Zhu, Junjia; Yang, Zhaohai; Sarwani, Nabeel; Li, Guangfu; Staveley-O’Carroll, Kevin F.; El-Deiry, Wafik S.

In: Cancer Biology and Therapy, Vol. 16, No. 5, 01.01.2015, p. 690-698.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Circulating tumor cell levels are elevated in colorectal cancer patients with high tumor burden in the liver

AU - Kaifi, Jussuf T.

AU - Kunkel, Miriam

AU - Dicker, David T.

AU - Joude, Jamal

AU - Allen, Joshua E.

AU - Das, Avisnata

AU - Zhu, Junjia

AU - Yang, Zhaohai

AU - Sarwani, Nabeel

AU - Li, Guangfu

AU - Staveley-O’Carroll, Kevin F.

AU - El-Deiry, Wafik S.

PY - 2015/1/1

Y1 - 2015/1/1

N2 - Background: Metastatic spread is the most common cause of cancer-related death in colorectal cancer (CRC) patients, with the liver being the mostly affected organ. Circulating tumor cells (CTCs) are a prognostic marker in stage IV CRC. We hypothesized that tumor burden in the liver correlates with CTC quantity. Methods: Blood (7.5 ml) was prospectively collected from 24 patients with novel stage IV CRC diagnosis. Baseline EpCAM+ CTCs were analyzed with the FDA-approved CellSearch® system. Clinicopathological data were collected, and hepatic tumor burden was determined by radiographic liver volumetry with contrast-enhanced CT scans. CRC primary tumors were immunohistochemically stained for EpCAM expression with BerEP4 monoclonal antibody. Statistical analyses were performed using 2-sample T-test, non-parametric Wilcoxon Rank-Sum test, and Fisher's exact test. Results: CTCs were detected n 17 (71%) of 24 patients. The overall mean CTC number as determined by EpCAM-based CellSearch® detection was 6.3 (SEM 2.9). High baseline CTC numbers (≥3) correlated significantly with a high tumor/liver ratio (≥30%), and with high serum CEA levels, as determined by two-sample T-test on log-transformed data and by Fisher's Exact test on categorical data analysis (P < 0.05). The CRC primary tumors were consistently expressing EpCAM by immunostaining. Conclusions: High tumor burden in the liver and high baseline serum CEA levels are associated with high number of baseline CTCs in stage IV CRC patients. Future studies should further investigate the biological role and expression patterns of single CTCs in cancer patients to further improve personalized treatment strategies.

AB - Background: Metastatic spread is the most common cause of cancer-related death in colorectal cancer (CRC) patients, with the liver being the mostly affected organ. Circulating tumor cells (CTCs) are a prognostic marker in stage IV CRC. We hypothesized that tumor burden in the liver correlates with CTC quantity. Methods: Blood (7.5 ml) was prospectively collected from 24 patients with novel stage IV CRC diagnosis. Baseline EpCAM+ CTCs were analyzed with the FDA-approved CellSearch® system. Clinicopathological data were collected, and hepatic tumor burden was determined by radiographic liver volumetry with contrast-enhanced CT scans. CRC primary tumors were immunohistochemically stained for EpCAM expression with BerEP4 monoclonal antibody. Statistical analyses were performed using 2-sample T-test, non-parametric Wilcoxon Rank-Sum test, and Fisher's exact test. Results: CTCs were detected n 17 (71%) of 24 patients. The overall mean CTC number as determined by EpCAM-based CellSearch® detection was 6.3 (SEM 2.9). High baseline CTC numbers (≥3) correlated significantly with a high tumor/liver ratio (≥30%), and with high serum CEA levels, as determined by two-sample T-test on log-transformed data and by Fisher's Exact test on categorical data analysis (P < 0.05). The CRC primary tumors were consistently expressing EpCAM by immunostaining. Conclusions: High tumor burden in the liver and high baseline serum CEA levels are associated with high number of baseline CTCs in stage IV CRC patients. Future studies should further investigate the biological role and expression patterns of single CTCs in cancer patients to further improve personalized treatment strategies.

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