Date: 10 Nov 2011
Prognostic Value of Putative Circulating Cancer Stem Cells in Patients Undergoing Hepatic Resection for Colorectal Liver Metastasis
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Although surgery is the gold standard treatment of hepatic metastasis from colorectal cancer (CRC), many patients ultimately die of their disease. We tested the hypothesis that the detection of circulating tumor cells (CTC) might identify patients at high risk of dying of disease recurrence after apparently radical liver surgery.
We considered 50 patients undergoing radical surgery for liver-confined hepatic metastasis from CRC. The expression of a panel of cancer-related genes, as assessed by quantitative real-time PCR, was used to detect CTC in the peripheral blood of these patients immediately before surgery. Survival analysis was performed by the Cox regression model.
Univariate analysis of the expression levels of CD133 (a marker of colon cancer stem cells) and survivin (an antiapoptotic factor) resulted in statistically significant association with patient survival [hazard ratio (HR) 2.7, 95% confidence interval (CI) 1.9–3.7, P < 0.0001; and hazard ratio 2.1, 95% CI 1.4–3.2, P < 0.0001, respectively]. Remarkably, multivariate analysis found that only the transcriptional amount of CD133 resulted in statistical significance (HR 2.6, 95% CI 1.9–3.6, P < 0.0001), indicating that this biomarker can independently predict the survival of these patients.
CD133-positive CTC may represent a suitable prognostic marker to stratify the risk of patients who undergo liver resection for CRC metastasis, which opens the avenue to identifying and potentially monitoring the patients who are most likely to benefit from adjuvant treatments.
Nelson R, Freels S. Hepatic artery adjuvant chemotherapy for patients having resection or ablation of colorectal cancer metastatic to the liver. Cochrane Database Syst Rev. 2006;(4):CD003770.
Kelley RK, Van Bebber SL, Phillips KA, Venook AP. Personalized medicine and oncology practice guidelines: a case study of contemporary biomarkers in colorectal cancer. J Natl Compr Canc Netw. 2010;9:13–25.
Grambsch TM, Therneau M. Modelling survival data. New York: Springer, 2000.
National Comprehensive Cancer Network. Colon cancer. National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology. http://www.nccn.org/.
Yu M, Stott S, Toner M, et al. Circulating tumor cells: approaches to isolation and characterization. J Cell Biol. 2010;192:373–82.CrossRef
Punnoose EA, Atwal SK, Spoerke JM, et al. Molecular biomarker analyses using circulating tumor cells. PLoS One. 2011;5:12517.
Todaro M, Francipane MG, Medema JP, Stassi G. Colon cancer stem cells: promise of targeted therapy. Gastroenterology. 2011;138:2151–62.CrossRef
Shmelkov SV, Butler JM, Hooper AT, et al. CD133 expression is not restricted to stem cells, and both CD133+ and CD133− metastatic colon cancer cells initiate tumors. J Clin Invest. 2008;118:2111–20.PubMed
Nakamura K, Iinuma H, Aoyagi Y, et al. Predictive value of cancer stem-like cells and cancer-associated genetic markers for peritoneal recurrence of colorectal cancer in patients after curative surgery. Oncology. 2011;78:309–15.CrossRef
Artells R, Moreno I, Diaz T, et al. Tumour CD133 mRNA expression and clinical outcome in surgically resected colorectal cancer patients. Eur J Cancer. 2011;46:642–9.CrossRef
Lugli A, Iezzi G, Hostettler I, et al. Prognostic impact of the expression of putative cancer stem cell markers CD133, CD166, CD44 s, EpCAM, and ALDH1 in colorectal cancer. Br J Cancer. 2011;103:382–90.CrossRef
Gazzaniga P, Gradilone A, Petracca A, et al. Molecular markers in circulating tumour cells from metastatic colorectal cancer patients. J Cell Mol Med. 2011;14:2073–7.CrossRef
- Prognostic Value of Putative Circulating Cancer Stem Cells in Patients Undergoing Hepatic Resection for Colorectal Liver Metastasis
Annals of Surgical Oncology
Volume 19, Issue 2 , pp 402-408
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- 1. Surgery Branch, Department of Oncological and Surgical Sciences, University of Padova, Padova, Italy
- 2. Istituto Oncologico Veneto (IOV-IRCCS), Padova, Italy