Department of Colorectal Surgery, The Affiliated Tumor Hospital of Harbin Medical University, Harbin, PR China.
J Surg Oncol. 2011 Mar 1;103(3):283-9. doi: 10.1002/jso.21802. Epub 2010 Dec 8.
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.
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.
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.
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.
本研究旨在阐明泛素羧基末端水解酶 22（USP22）的表达，USP22 是一种新的去泛素化酶基因，在结直肠癌（CRC）及其临床意义中。
采用定量 RT-PCR、Western blot 和免疫组织化学（IHC）检测 43 例 CRC 及配对非癌组织中 USP22 的表达。进一步通过 IHC 分析 192 例 CRC 肿瘤中 USP22 蛋白表达，评估其与生存的关系。
在 43 对新鲜组织中，USP22 的表达水平在原发性 CRC 组织中明显高于配对非癌组织，无论是在 mRNA 水平还是在蛋白水平（P < 0.0001）。USP22 核表达从正常黏膜经腺瘤到原发性癌（P < 0.0001），再从原发性癌到肝转移（P = 0.021）呈显著升高。在 192 例常规 CRC 组织中，USP22 阳性表达的发生率为 54.16%。值得注意的是，USP22 高表达与较短的疾病特异性生存（P < 0.0001）和较短的无病生存（P < 0.0001）显著相关。Cox 回归分析显示，USP22 是 CRC 患者的独立预后参数。
USP22 可能是 CRC 预后的独立预测因子，USP22 的异常表达可能在结直肠发生和肝转移中发挥重要作用。
