Department of Surgery, Seoul National University Hospital, Seoul, Korea.
Cancer Res Treat. 2010 Sep;42(3):151-6. doi: 10.4143/crt.2010.42.3.151. Epub 2010 Sep 30.
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.
We examined the regulation and clinical significance of RhoGDI2 in Korean breast cancer patients by using proteomic approaches.
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).
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.
最近的研究已经确定了许多在各种癌症的系统性转移过程中发挥特定作用的基因和蛋白质。Rho GDP 解离抑制剂 2(RhoGDI2)已被证明可抑制人类膀胱癌的转移,但它在乳腺癌中的作用存在争议。
我们使用蛋白质组学方法研究了 RhoGDI2 在韩国乳腺癌患者中的调控和临床意义。
通过蛋白质组学方法,我们观察到 RhoGDI2 在人乳腺癌组织中的表达高于正常乳腺组织,并在 8 例乳腺癌患者的独立队列中验证了其上调。通过免疫组织化学方法在 57 例乳腺癌患者中研究了 RhoGDI2 表达的临床意义。RhoGDI2 与肿瘤大小、淋巴结转移、组织学分级或激素受体状态均无显著相关性。然而,具有 RhoGDI2 表达肿瘤的患者无病生存期(p=0.043;风险比,3.87)和远处转移无复发生存期(p=0.039;风险比,5.15)明显缩短。
我们的研究结果表明 RhoGDI2 可能是一种预后不良的标志物,也是一种潜在的治疗靶点。RhoGDI2 在我们的研究中表现出促转移的特性,这可能表明它在癌症转移中具有器官特异性的作用。