Aberrant Expression of USP22 is Associated With Liver Metastasis and Poor Prognosis of Colorectal Cancer

Background: The present study was aimed at clarifying the expression of ubiquitin carboxyl-terminal hydrolase 22 (USP22), a novel deubiquitinating enzyme gene, in colorectal cancer (CRC) and its clinical significance. Methods: USP22 expression was detected with quantitative RT-PCR. Western blot, and immunohistochemistry (IHC) in 43 CRCs and non-cancerous matched tissues. Furthermore, USP22 protein expression was analyzed in 192 CRC tumors by IHC to evaluate the association with survival. Results: In 43 paired fresh tissues, the expression level of USP22 was significantly higher in primary CRCs than that in the paired non-cancerous tissues at both mRNA and protein levels (P < 0.0001). Nuclear USP22 expression significantly increased from normal mucosa through adenoma to primary carcinoma (P < 0.0001) and from primary carcinoma to liver metastasis (P = 0.021). The incidence of positive USP22 expression was 54.16% in 192 conventional CRC tissues. Notably, high USP22 expression was significantly associated with shorter disease-specific survival (P < 0.0001) and shorter disease-free survival (P < 0.0001). Cox regression analysis showed USP22 was an independent prognostic parameter for CRC patients. Conclusion: USP22 might be an independent predictive factor for CRC prognosis and aberrant expression of USP22 may play an essential role in colorectal carcinogenesis and liver metastasis. J. Surg. Oncol. 2011:103:283-289. (C) 2010 Wiley-Liss, Inc.