Up-regulation of Tiam1 and Rac1 Correlates with Poor Prognosis in Hepatocellular Carcinoma

T-cell lymphoma invasion and metastasis 1 (Tiam1) specifically activates Rho-like GTPases (e.g. Rac1) and Tiam1-Rac1 pathway affects the migration and invasion of many tumors, such as nasopharyngeal carcinoma, breast cancer and retinoblastoma. However, no studies have yet comprehensively examined the involvement of Tiam1-Rac1 pathway in hepatocellular carcinoma. In this study, we examined the relationship of the up-regulation of Tiam1 and Rac1 with clinicopathological features in patients with hepatocellular carcinoma. Expression of Tiam1 and Rac1 was assessed in 242 hepatocellular carcinoma tissues and their adjacent normal hepatic tissues by performing immunohistochemistry and was gauged regarding stage, grade and survival. Immunohistochemistry showed that patients with a high clinical stage hepatocellular carcinoma (III-IV) and alpha-fetoprotein levels had a higher tendency to express Tiam1 and Rac1 on tumor cells than the patients with low pathologic grade hepatocellular carcinoma (I-II) (P = 0.008 and 0.01, respectively) and low alpha-fetoprotein levels (P = 0.006 and 0.002, respectively). In addition, Tiam1 and Rac1 up-regulation was also significantly associated with vascular invasion status (both P = 0.02), intrahepatic metastasis status (P = 0.009 and 0.01, respectively) and histological differentiation (P = 0.008 and 0.009, respectively) of patients with hepatocellular carcinoma. Moreover, post-operative survival analysis indicated that hepatocellular carcinoma patients with strong Tiam1 (P = 0.01) and Rac1 (P = 0.02) expression had shorter disease-specific survival than those with weak expression. Multivariate analysis also showed that Tiam1 and Rac1 overexpression could be two predictors of poor prognosis (P = 0.02 and 0.03, respectively). The current study demonstrated for the first time that the Tiam1-Rac1 pathway may play a critical role in tumor progression of hepatocellular carcinoma. The expression of Tiam1 and Rac1 can be considered as the two useful indicators for predicting the prognosis of hepatocellular carcinoma.