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Clinical and Prognostic Significance of RhoA and RhoC Gene Expression in Esophageal Squamous Cell Carcinoma

¹ Department of General Surgical Science (Surgery I), Gunma University, 3-39-22, Showa-machi, Maebashi, Gunma 371-8511, Japan
² Department of Surgery, Padjadjaran University Faculty of Medicine, 38 Pasteur Street, Bandung, West Java 40161, Indonesia
³ Department of Gynecology and Reproductive Medicine, Gunma University, 3-39-22, Showa-machi, Maebashi, Gunma 371-8511, Japan

Correspondence: Address correspondence and reprint requests to: Ahmad Faried, MD, PhD; E-mail: afaried{at}med.gunma-u.ac.jp

Background: Rho GTPases are involved in the organization of a microfilament network, cell-to-cell interaction, and malignant transformation. To elucidate the role of Rho GTPases in esophageal squamous cell carcinoma (ESCC), we compared the levels of RhoA and RhoC mRNA from ESCC with the corresponding normal tissue originating from the same patients.

Methods: Real-time reverse transcriptase–polymerase chain reaction was performed to observe rhoA and rhoC in esophageal cell lines. Next, the mRNA levels of rhoA and rhoC were evaluated from 50 patients.

Results: The rhoA and rhoC were higher in ESCC cell lines than in noncancerous esophageal cell. rhoC was overexpressed in TTn, which was obtained directly from a surgical specimen of a metastatic lesion of ESCC in the mandible. rhoA and rhoC were significantly higher in ESCC patient than in the normal counterparts (P = .0022 and P < .0001, respectively). rhoA correlated with tumor differentiation and rhoC correlated with an advanced tumor, node, metastasis system classifications. rhoA and rhoC in ESCC showed a positive correlation (P = .008). Patients with rhoA overexpression showed a significantly poorer prognosis than those with rhoA underexpression (P = .044).

Conclusions: To our knowledge, this study is the first in which the expression of RhoA and RhoC at the mRNA level in ESCC was examined and compared with its normal counterpart. Our results suggest that rhoA and rhoC are involved in ESCC progression and useful as prognostic markers. Further study will be needed to examine the therapeutic potential of the Rho GTPase inhibitor as a promising anticancer therapy, especially in ESCC.

Key Words: Esophageal squamous cell carcinoma • rhoA • rhoC • Prognostic marker