Identification of CD206 as a potential biomarker of cancer stem-like cells and therapeutic agent in liver cancer.

The mannose receptor (CD206) functions in endocytosis and phagocytosis, and plays an important role in immune homeostasis. Tumor-associated macrophages express high level of CD206 and are thought to contribute to cancer progression through tumor immunosuppression, metastasis and angiogenesis. However, the significance of CD206 in the pathology of liver cancer has not been investigated. The present study evaluated the clinical significance of CD206 in the progression and prognosis of liver cancer in pathological tissues from 327 patients. Increased CD206 expression was observed in liver cancer samples compared with healthy adjacent liver tissue (42.8 vs. 62.4%; P<0.05). CD206 expression was significantly associated with tumor size (P=0.009) and metastasis (P=0.041). The recurrence free survival rate of patients with CD206-positive liver cancer was significantly decreased compared with patients with CD206-negative liver cancer (P=0.003). A Cox regression model revealed that liver cancer survival was independently associated with tumor size, metastasis and α-fetoprotein value. The results further revealed that CD206 expression in cancer stem cell (CSC)-like cells was comparable to other internationally recognized biomarkers. Additionally, when CD206 expression was silenced in the liver cancer cell lines HepG2 and PLC/PRF/5 using a short hairpin RNA approach, migration and invasion of the cells significantly decreased compared with controls (P<0.01). CD206 expression in liver cancer significantly influences distant metastasis and spread, resulting in poor patient prognosis. Furthermore, CD206 may be a potential biomarker in CSC-like cells to predict the occurrence of liver cancer.