Lgr5 is a potential marker of colorectal carcinoma stem cells that correlates with patient survival

Background: Lgr5 (leucine-rich-repeat-containing G-protein-coupled receptor 5) has recently beenidentified as an intestinal stem cell marker. In order to determine whether Lgr5 is a potentialmarker of cancer stem cells, we investigated whether Lgr5 expression correlated with Ki-67expression and prognosis in colorectal carcinoma. Methods: Lgr5 and Ki-67 expression were evaluated by immunohistochemistry in 192 colorectalcarcinoma specimens. Selection of side population (SP) cells was performed by staining withHoechest 33342, and Lgr5 expression in Colo205 SP cells was then detected byimmunofluorescence. Results: Lgr5 expression was significantly higher in carcinoma than in normal mucosa (P=0.001).Lgr5 was positively correlated with histological grade (P=0.001), depth of invasion(P=0.001), lymph node metastasis (P=0.001), distant metastasis (P=0.004), pTNM stage(P=0.001), and Ki-67 (r=0.446, P=0.001). Multivariate analysis showed that the effect ofLgr5 on survival was independent of Ki-67 (P=0.037). In the in vitro study, Hoechst lowstainingcells were counted in 7% of the Colo205 colon cancer cell line population, and Lgr5expression was strikingly stronger in Hoechst low-staining cells than in high-staining cells(P=0.001). Conclusions: These findings suggest that Lgr5 may play an important role in the progression and prognosisof colorectal carcinoma, and may be a potential new therapeutic target for the treatment ofcolorectal cancer patients. It may also be considered as a potential marker for colorectalcancer stem cells (CSCs).

via World Journal of Surgical Oncology