Expression of Lgr5, a marker of intestinal stem cells, in colorectal cancer and its clinicopathological significance

摘要

Cancer stem cells (CSCs) have been the focus of intense investigations in cancer research although the cellular origin of CSCs has not been clearly determined. Lgr5 is a regulated target of Wnt/β-catenin signaling, which was first identified as a marker of intestinal stem cells. However, the expression of Lgr5 in human colorectal cancer (CRC) and its clinical clinicopathological significance in CRC patients as well as its correlation with Wnt/β-catenin pathway are not fully explored. Localization and expression of Lgr5 in CRC tissues was performed by immunohistochemical staining. The correlation between its expression levels and clinicopathological features as well as clinical outcomes of patients was analysed. The quantitative expression levels of Lgr5 in various CRC cell lines were determined using real-time RT-PCR. The relationship between Lgr5 expression and Wnt/β-catenin pathway in CRC was also investigated. Obviously elevated expression of Lgr5 was observed in CRC tissues, compared to the paired nontumor tissues. mRNA expression levels of Lgr5 was positively correlated with the expression of β-catenin in CRC tissues. The expression of Lgr5 was various in different CRC cell lines. Low and high expression levels of Lgr5 were significantly correlated with clinicopathological features such as TNM stage, lymph node metastasis and vascular invasion of CRC patients. More importantly, Lgr5 expression in CRC tissues was also associated with tumor angiogenesis as well as clinical outcomes. Taken together, these results suggest that elevated Lgr5 expression might contribute to the development and progression of CRC, and it could also be used a potential unfavorable prognostic biomarker for CRC. A better understanding of molecule mechanisms and the relevance of potential value for Lgr5 in the progression of CRC will help to identify a novel therapeutic strategy for CRC patients.