Abstract
The significance of cancer stem cells (CSCs) in initiation and progression of colon cancer (CC) has been established. In this study, we investigated the utility of measuring mRNA expression levels of CSC markers EpCAM, LGR5 and LGR4 for predicting survival outcome in surgically treated CC patients. Expression levels were determined in 5 CC cell lines, 66 primary CC tumors and 382 regional lymph nodes of 121 CC patients. Prognostic relevance was determined using Kaplan-Meier survival and Cox regression analyses. CC patients with lymph nodes expressing high levels of EpCAM, LGR5 or LGR4 (higher than a clinical cutoff of 0.07, 0.06 and 2.558 mRNA copies/18S rRNA unit, respectively) had a decreased mean survival time of 32 months for EpCAM and 42 months for both LGR5 and LGR4 at a 12-year follow-up (p = 0.022, p = 0.005 and p = 0.011, respectively). Additional patients at risk for recurrence were detected when LGR5 was combined with the biomarkers CXCL17 or CEA plus CXCL16. In conclusion, the study underscores LGR5 as a particularly useful prognostic biomarker and illustrates the strength of combining biomarkers detecting different subpopulations of cancer cells and/or cells in the tumor microenvironment for predicting recurrence.
Highlights
Cancer stem cells (CSCs) constitute a subpopulation of cancer cells with self-renewal and multi-lineage differentiation capabilities [1]
We investigated the prognostic value of measuring the mRNA expression levels of the CSC markers epithelial cell adhesion molecule (EpCAM), leucine-rich repeatcontaining G protein-coupled receptor 5 (LGR5) and LGR4 in primary tumors and regional lymph nodes of CC patients
The mRNA levels of EpCAM and LGR5 but not LGR4 were significantly higher in primary tumors than in normal colon tissues
Summary
Cancer stem cells (CSCs) constitute a subpopulation of cancer cells with self-renewal and multi-lineage differentiation capabilities [1]. CSC associated with different malignancies can be identified through their expression of specific biomarkers. A number of CSC markers linked to colorectal cancer (CRC) have been described, including, but not restricted to, epithelial cell adhesion molecule (EpCAM), and leucine-rich repeatcontaining G protein-coupled receptor 5 (LGR5) [2,3]. EpCAM is a transmembrane protein expressed by normal epithelial cells and cancers of epithelial origin. In addition to its role in intercellular adhesion, EpCAM functions in cell signaling, differentiation, proliferation and migration [4]. In CRC, the capability of cancer cells isolated from primary tumors to form xenografts when injected in immunodeficient mice was reserved to a small subset of cells showing EpCAMhigh /CD44+
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
