RhoE is Associated with Relapse and Prognosis of Patients with Colorectal Cancer

Abstract

RhoE, an atypical Rho protein, is differently deregulated in some solid tumors, and there are conflicting data describing the role of RhoE in tumor cell migration and invasion. This study aimed to investigate RhoE expression in human colorectal cancer and its relationship with clinicopathological features and prognosis. Colorectal cancer and adjacent normal tissues from 202 patients were examined by immunohistochemistry. Staining evaluation results were analyzed statistically in relation to various clinicopathological parameters, disease-free survival, and overall survival. RhoE expression was also investigated by immunohistochemistry in 80 node metastases and the corresponding primary lesions, and by Western blot test in six cancer and adjacent normal tissues. The relationship between RhoE and invasion was examined by transwell assay and Western blot test. The positive rate for RhoE in colorectal cancer was significantly higher than that of normal colorectal tissues. In colorectal cancer, RhoE expression was significantly correlated with depth of invasion, lymph node metastasis, and distant metastasis. Consistently, overexpression of RhoE in SW620 cells up-regulated vimentin, down-regulated E-cadherin, increased the expression of matrix metalloproteinase (MMP) 9, and enhanced cell invasion in vitro; in contrast, silencing of RhoE by a specific siRNA caused opposite effects. Most importantly, disease-free and overall survivals were significantly poorer for patients with RhoE-positive tumors than for those with RhoE-negative tumors. These findings emphasize the positive role of RhoE in invasion and metastasis in human colorectal cancer. It could also serve as an independent prognostic marker in addition to the tumor, node, metastasis staging system.