Cancer Res Treat.  2010 Sep;42(3):151-156.

Up-regulation of RhoGDI2 in Human Breast Cancer and Its Prognostic Implications

• Moon HG
• Jeong SH
• Ju YT
• Jeong CY
• Lee JS
• Lee YJ
• Hong SC
• Choi SK
• Ha WS
• Park ST
• Jung EJ

Abstract

PURPOSE
Recent research has identified many genes and proteins that play specific roles in the process of systemic metastasis in various types of cancer. Rho GDP dissociation inhibitor 2 (RhoGDI2) has been shown to inhibit metastasis in human bladder cancer, but its role in breast cancer is controversial.
MATERIALS AND METHODS
We examined the regulation and clinical significance of RhoGDI2 in Korean breast cancer patients by using proteomic approaches.
RESULTS
By using a proteomic approach, we observed an increased expression of RhoGDI2 in human breast cancer tissues when compared to that of the normal breast tissues, and we validated its up-regulation in an independent cohort of 8 breast cancer patients. The clinical implication of a RhoGDI2 expression was investigated in 57 breast cancer patients by performing immunohistochemistry. RhoGDI2 did not show a significant association with the tumor size, lymph node metastasis, the histologic grade or the hormone receptor status. However, the patients with RhoGDI2-expressing tumors had significantly shorter disease-free survival (p=0.043; hazard ratio, 3.87) and distant metastasis-free survival (p=0.039; hazard ratio, 5.15).
CONCLUSION
Our results demonstrated a potential role of RhoGDI2 as a poor prognostic marker as well as a potential therapeutic target. The pro-metastatic nature of RhoGDI2 shown in our study may indicate its organ-specific role in cancer metastasis.

Keyword

Breast neoplasms; RhoGDI2 protein; Prognosis; Neoplasm metastasis; Proteomics

MeSH Terms

Breast
Breast Neoplasms
Cohort Studies
Disease-Free Survival
Humans
Immunohistochemistry
Lymph Nodes
Neoplasm Metastasis
Prognosis
Proteins
Proteomics
rho Guanine Nucleotide Dissociation Inhibitor beta
Up-Regulation
Urinary Bladder Neoplasms
Proteins
rho Guanine Nucleotide Dissociation Inhibitor beta

Figure

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  Fig. 1 Images of the 2-dimensional electrophoresis (DE) gels of the cancerous and non-cancerous tissues showing increased expression of Rho GDP dissociation inhibitor 2 (RhoGDI2; circle and arrow) (A), and magnified images of the spot representing RhoGDI2 in 6 breast cancer patients (B).

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  Fig. 2 Results of western blotting using and additional 8 invasive ductal carcinoma patients (A) and densitometry results (B).

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  Fig. 3 Immunohistochemical staining for Rho GDP dissociation inhibitor 2 (RhoGDI2) in the human breast cancer tissues RhoGDI2 showed differential expression patterns in the human breast cancer tissues (×400). RhoGDI2 showed both a cytoplasmic expression and a nuclear expression in the human breast cancer tissue; the positive RhoGDI2 expression in 34 patients (A) and the negative RhoGDI2 expression in 23 patients (B).

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  Fig. 4 Results of the survival analysis according to the Rho GDP dissociation inhibitor 2 (RhoGDI2) expression The survival curves of the Cox proportional hazard regression analysis show a difference of survival according to the RhoGDI2 expression in terms of disease-free survival (A) and distant metastasis-free survival (B). The adjusted covariates are tumor size, the presence of lymph node metastasis, the histologic grade and the estrogen receptor status. HR, hazard rate; CI, confidence interval.

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