The Expression And Clinical Significance Of EpCAM^high /CD44⁺ Colorectal Cancer Stem Cells And β-catenin In Colorectal Cancer

Background: Colorectal cancer is one of the most common malignant tumor. Its incidence and mortality rates increase rapidly, and 20-40 percent of patients have liver metastases at the time of diagnosis. Recurrence and metastasis is the major problem of treatment failure in colorectal cancer. One important reason is that there are a few tumor cells with self-renewal, differentiation potential, multi-drug resistance and tumorigenesis characteristics, which is called cancer stem cells. These cells lead to the recurrence and metastasis of tumor. Wnt signalling pathway plays an important role in maintaining these characteristics of cancer stem cells. When the key proteinβ-catenin in Wnt signalling pathway is abnormally activated, the colorectal cancer stem cells has the dysfunction of self-renewal and differentiation inhibition, which led to the genesis of the tumor. Thus it is significance to explore the interaction between Wnt signalling pathway and colorectal cancer stem cells which lead to recurrence and metastasis .Objective: To explore the effect of Wnt signalling pathway in the maintenance, invasion and metastasis of colorectal cancer stem cells.Methods: Double immunohistochemical staining was used to detect the expression of EpCAM^high/CD44⁺ which is regarded as the marker of colorectal cancer stem cells in 80 cases of colorectal cancer and their corresponding liver metastases. The SP method of immunohistochemistry was used to detect the expression ofβ-catenin in these tissue. The expression and correlation ofβ-catenin and EpCAM^high/CD44⁺ in colorectal cancer were analyzed to explore the effect of Wnt signalling pathway in the maintenance, invasion and metastasis of colorectal cancer stem cells. Results:1.In the 80 cases of colorectal cancer and their corresponding liver metastases, the abnormal expression ofβ-catenin has no correlation with gender, age and the magnitude of the tumor (P>0.05), but it is significantly correlated with degree of differentiation, depth of invasion, clinical stage and metastasis (P<0.05). In the corresponding liver metastases, the abnormal expression ofβ-catenin is also higher.2. In the 80 cases of colorectal cancer and their corresponding liver metastases, the expression of EpCAM^high/CD44⁺-double-positive cells has no correlation with gender and the magnitude of the tumor (P>0.05), but it is significantly correlated with age, degree of differentiation, depth of invasion, clinical stage and metastasis (P<0.05). In the corresponding liver metastases, we can also detecte EpCAM^high/CD44⁺ cells.3.In 44 cases with abnormal expression ofβ-catenin, the expression rate of EpCAM^high/CD44⁺ is 84.1%, which is significantly higher than 44.4% in those cases with normal expression ofβ-catenin. By Pearson correlation analysis, there is significant correlation betweenβ-catenin and EpCAM^high/CD44⁺ expression (P = 0.000, r = 0.417), and the difference is statistically significant.Conclusion:1.The abnormal expression of the key proteinβ-catenin in Wnt signalling pathway is significantly correlated with degree of differentiation, depth of invasion, clinical stage and metastasis. It is involved in the genesis and metastasis of tumors. It also can be regarded as an important reference for judging whether the colorectal cancer has the malignant potential.2.The expression of EpCAM^high/CD44⁺ has significant correlation with age, degree of differentiation, depth of invasion, clinical stage and metastasis. In the corresponding liver metastases, we can also detecte EpCAM^high/CD44⁺ cells,indicating colorectal cancer stem cells may have the characteristics of invasion and metastasis and lead to recurrence and metastasis in colorectal cancer.3.There are significant correlation between the key proteinβ-catenin in Wnt signalling pathway and the colorectal cancer stem cells marker EpCAM^high/CD44⁺, and both of them are significantly correlated with the invasion and metastasis. Thus we deduce the abnormal activation of Wnt signalling pathway prompt the abnormal proliferation of the colorectal cancer stem cells, which leads to the recurrence and metastasis of the cancer.