Prognostic Value of Putative Circulating Cancer Stem Cells in Patients Undergoing Hepatic Resection for Colorectal Liver Metastasis

• Published in: Annals of surgical oncology Vol. 19; no. 2; pp. 402 - 408
• Main Authors: Pilati, Pierluigi, Mocellin, Simone, Bertazza, Loris, Galdi, Francesca, Briarava, Marta, Mammano, Enzo, Tessari, Emanuela, Zavagno, Giorgio, Nitti, Donato
• Format: Journal Article
• Language: English
• Published: New York Springer-Verlag 01-02-2012; Springer Nature B.V
• Subjects: Aged; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Colorectal Cancer; Colorectal Neoplasms - mortality; Colorectal Neoplasms - pathology; Colorectal Neoplasms - surgery; Female; Follow-Up Studies; Hepatectomy; Humans; Liver Neoplasms - mortality; Liver Neoplasms - secondary; Liver Neoplasms - surgery; Lymphatic Metastasis; Male; Medicine; Medicine & Public Health; Middle Aged; Neoplasm Recurrence, Local - diagnosis; Neoplasm Recurrence, Local - mortality; Neoplasm Recurrence, Local - surgery; Neoplasm Staging; Neoplastic Cells, Circulating - metabolism; Neoplastic Cells, Circulating - pathology; Neoplastic Stem Cells - metabolism; Neoplastic Stem Cells - pathology; Oncology; Prognosis; Real-Time Polymerase Chain Reaction; Retrospective Studies; Reverse Transcriptase Polymerase Chain Reaction; Surgery; Surgical Oncology; Survival Rate; Liver Metastasis; Colorectal Liver Metastasis; Epithelial Growth Factor Receptor; Vascular Endothelium Growth Factor; Circulate Tumor Cell
• DOI: 10.1245/s10434-011-2132-2
• EISSN: 1534-4681
• ISSN: 1068-9265

Background
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.
Methods
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.
Results
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.
Conclusions
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.