Clinical and prognostic significance of RhoA and RhoC gene expression in esophageal squamous cell carcinoma

Ann Surg Oncol. 2007 Dec;14(12):3593-601. doi: 10.1245/s10434-007-9562-x. Epub 2007 Sep 25.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / metabolism
  • Cell Differentiation
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / metabolism
  • Esophagus / cytology
  • Esophagus / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Prognosis
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Survival
  • Tumor Cells, Cultured
  • rho GTP-Binding Proteins / genetics*
  • rho GTP-Binding Proteins / metabolism
  • rhoA GTP-Binding Protein / genetics*
  • rhoA GTP-Binding Protein / metabolism
  • rhoC GTP-Binding Protein

Substances

  • RNA, Messenger
  • RNA, Neoplasm
  • RHOA protein, human
  • RHOC protein, human
  • rho GTP-Binding Proteins
  • rhoA GTP-Binding Protein
  • rhoC GTP-Binding Protein