Department of Surgery, Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo, 105-8461, Japan.
Int J Clin Oncol. 2012 Apr;17(2):137-42. doi: 10.1007/s10147-011-0270-y. Epub 2011 Jun 24.
Small GTPase proteins, including RhoA, RhoB, RhoC, Rac1, and cdc42, are important molecules for linking cell shape and cell-cycle progression because of their role in both cytoskeletal arrangements and mitogenic signaling. Over-expression of wild-type or constitutively active forms of RhoA has been shown to induce invasive behavior in non-invasive rat hepatoma cells in vitro. In addition, over-expression of RhoC has been found in melanoma cells with increasing metastatic activity as well as inflammatory breast cancer. These results indicate that overexpression of Rho proteins contributes to cancer cell invasion and metastasis. Rho GDP dissociation inhibitor 2 (RhoGDI2) was recently shown to act as a metastasis suppressor gene in bladder cancer. The purpose of this study was to clarify the clinical significance of this gene expression in patients with colorectal carcinoma.
Fifty pairs of normal mucosa and cancer specimens obtained at the time of surgery from patients with colorectal cancer (CRC) were subjected to reverse transcription-polymerase chain reaction for RhoGDI2.
No patients with RhoGDI2-higher expression tumors had liver metastasis (0 in 8 cases); however, 33.3% (14 in 42 cases) of patients with RhoGDI2-lower expression tumors had liver metastasis. With regard to outcome in relation to RhoGDI2-positivity, RhoGDI2-higher expression tumors had a significant correlation with superior relapse-free survival (RFS) time as compared to RhoGDI2-lower expression tumors in stage III CRC (log-rank test, P < 0.05). Moreover, multivariate analysis indicated that RhoGDI2 was an independent prognostic factor for RFS.
RhoGDI2 is a novel predictor of RFS in patients with colorectal carcinoma.
小 GTP 酶蛋白，包括 RhoA、RhoB、RhoC、Rac1 和 cdc42，是连接细胞形态和细胞周期进程的重要分子，因为它们在细胞骨架排列和有丝分裂信号中都有作用。已经表明，野生型或组成性激活形式的 RhoA 的过表达可在体外诱导非侵袭性大鼠肝癌细胞的侵袭行为。此外，在具有增加的转移活性的黑色素瘤细胞以及炎症性乳腺癌中发现了 RhoC 的过表达。这些结果表明 Rho 蛋白的过表达有助于癌细胞的侵袭和转移。Rho GDP 解离抑制剂 2（RhoGDI2）最近被证明在膀胱癌中作为转移抑制基因发挥作用。本研究的目的是阐明该基因在结直肠癌患者中的表达的临床意义。
对 50 对手术时获得的结直肠癌患者的正常黏膜和癌组织进行 RhoGDI2 的逆转录聚合酶链反应。
在 RhoGDI2 高表达肿瘤的患者中没有发生肝转移（8 例中有 0 例）；然而，在 RhoGDI2 低表达肿瘤的患者中，有 33.3%（42 例中有 14 例）发生了肝转移。在 RhoGDI2 阳性与结局的关系方面，在 III 期结直肠癌中，RhoGDI2 高表达肿瘤的无复发生存时间（RFS）与 RhoGDI2 低表达肿瘤相比具有显著相关性（对数秩检验，P < 0.05）。此外，多因素分析表明 RhoGDI2 是 RFS 的独立预后因素。
RhoGDI2 是结直肠癌患者 RFS 的一个新的预测因子。
