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

Abstract

BACKGROUND: Lgr5 (leucine-rich-repeat-containing G-protein-coupled receptor 5) has recently been identified as an intestinal stem cell marker. In order to determine whether Lgr5 is a potential marker of cancer stem cells, we investigated whether Lgr5 expression correlated with Ki-67 expression and prognosis in colorectal carcinoma. METHODS: Lgr5 and Ki-67 expression were evaluated by immunohistochemistry in 192 colorectal carcinoma specimens. Selection of side population (SP) cells was performed by staining with Hoechest 33342, and Lgr5 expression in Colo205 SP cells was then detected by immunofluorescence. 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 of Lgr5 on survival was independent of Ki-67 (P=0.037). In the in vitro study, Hoechst low-staining cells were counted in 7% of the Colo205 colon cancer cell line population, and Lgr5 expression 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 prognosis of colorectal carcinoma, and may be a potential new therapeutic target for the treatment of colorectal cancer patients. It may also be considered as a potential marker for colorectal cancer stem cells (CSCs).