Overexpression of CD151 as an Adverse Marker for Intrahepatic Cholangiocarcinoma Patients

BACKGROUND: Previous studies have indicated that CD151, a hydrophobic protein, forms a functional complex with the proto-oncogene that encodes an N-methyl-N'-nitro-N-nitroso-guanidine (MET) protein (c-Met), and CD151 overexpression reportedly is involved in metastasis/invasion of several tumors. The objective of the current study was to investigate the expression and role of CD151 and/or c-Met in intrahepatic cholangiocarcinoma (ICC). METHODS: Sixty ICC tissues with matched nontumorous tissues and 20 normal liver tissues were used to analyze CD151 expression at the level of messenger RNA (mRNA) and protein. Then, the expression of CD151 in an ICC cell line was interrupted using a specific lentiviral-mediated small hairpin RNA (shRNA)-CD151, and the role of CD151 in the proliferation, metastasis, and invasion of ICC cells was assessed. The expression of CD151/c-Met was examined further by immunohistochemistry in a tissue microarray (TMA) that included 140 samples of ICC, and the prognostic role of CD151 and/or c-Met in ICC was evaluated in Kaplan-Meier and Cox regression analyses. RESULTS: The expression of CD151 in ICC tissues was much higher than that in nontumorous samples and normal liver; and, after the down-regulation of CD151, HCCC-9810 cells had decreased capability for metastasis/invasion in vitro. CD151 overexpression was correlated significantly with larger tumors, poor differentiation, multiple nodular, microvascular/bile duct invasion, and lymphatic metastasis (P<.05). The postoperative 2-year and 5-year overall survival (OS) rates for patients with low CD151 expression (<50% tumor staining) and/or low c-Met expression (<20% tumor staining) were higher than the rates for patients with high CD151 expression (>= 50% tumor staining) and/or high c-Met expression (>= 20% tumor staining). Multivariate analysis revealed that CD151 overexpression and c-Met overexpression were independent prognostic markers for ICC. CONCLUSIONS: Overexpression of CD151 was implicated in metastasis/invasion of ICC, and both CD151 overexpression and c-Met overexpression may be potential molecular therapeutic targets for ICC. Cancer 2010;116:5440-51. (C) 2010 American Cancer Society.