Expression of stem cell markers CD44 and Lgr5 in colorectal cancer and its relationship with lymph node and liver metastasis

Abstract

Objective: To investigate the relationship between the expression of stem cell markers CD44 and Lgr5 and the clinicopathological features, lymph node and liver metastasis, and to analyse the value of both in evaluating the prognosis of colorectal cancer. Methods: A total of 90 cases of colorectal cancer, 20 cases of adjacent tissues, 30 cases of lymph node metastases, 28 cases of cancer nodules and 30 cases of liver metastasis of colorectal cancer were collected from Department of Pathology of the Second Hospital of Tianjin Medical University from January 2011 to June 2016. The expression of CD44 and Lgr5 protein was detected by immunohistochemistry, and the relationship between them and clinical pathological data, lymph node metastasis and liver metastasis were analyzed. Results: The positive expression rates of CD44 and Lgr5 in colorectal cancer tissues were 68.9% and 62.2%, which were significantly higher than 30.0% and 15.0% of adjacent tissues(P=0.001 and P<0.001). The expression of CD44 and Lgr5 in colorectal cancer was associated with histological differentiation, depth of tumor invasion, lymph node metastasis, soft tissue nodules, hepatic metastasis, and TNM staging(P=0.021, 0.032, 0.030, 0.011, 0.015, 0.007 and P=0.011, 0.027, 0.017, 0.008, 0.011, 0.021). The positive rates of CD44 and Lgr5 expression in lymph node metastases, cancer nodules and liver metastases (93.3%, 89.3%, 90.0%, and 83.3%, 89.3%, 86.7%) were higher than those in the primary lesions(68.9% and 62.2%)(P=0.007, 0.032, 0.022 and P=0.033, 0.007, 0.013). There is a positive correlation between the expression of CD44 and Lgr5 in colorectal cancer(r=0.615, P<0.001), and both positive expression of CD44 and Lgr5 is associated with histological differentiation, lymph node metastasis and cancer nodules, liver metastasis and TNM staging(P=0.005, 0.003, 0.003, 0.026, 0.014). The Kaplan-Meier survival curve showed that the survival rate of positive expression of CD44 and both positive expression of CD44 and Lgr5 in patients with colorectal cancer was low(P=0.030 and 0.001). Log-rank univariate survival analysis showed that histological differentiation, depth of invasion, lymph node metastasis, liver metastasis, and clinical stage were the influencing factors of postoperative survival time(P=0.035, 0.035, 0.018, 0.016, 0.004). Cox proportional hazards regression model multivariate analysis showed that both positive expression of CD44 and Lgr5, lymph node metastasis, liver metastasis, and clinical stage were independent factors affecting the prognosis of patients with colorectal cancer(P=0.004, 0.044, 0.031, 0.008). Conclusions: The expression of CD44 and Lgr5 is related to the malignant biological behavior of colorectal cancer, and they are important factors in promoting local and distant metastases. Both positive expression of them have a hint of bad prognosis.