Faried Ahmad, Faried Leri S, Usman Nurhayat, Kato Hiroyuki, Kuwano Hiroyuki
Department of General Surgical Science (Surgery I), Gunma University, 3-39-22, Showa-machi, Maebashi, Gunma, 371-8511, Japan.
Ann Surg Oncol. 2007 Dec;14(12):3593-601. doi: 10.1245/s10434-007-9562-x. Epub 2007 Sep 25.
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.
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.
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).
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.
Rho GTP酶参与微丝网络的组织、细胞间相互作用及恶性转化。为阐明Rho GTP酶在食管鳞状细胞癌（ESCC）中的作用，我们比较了ESCC患者的RhoA和RhoC mRNA水平与来自同一患者的相应正常组织的水平。
采用实时逆转录聚合酶链反应观察食管癌细胞系中的rhoA和rhoC。接下来，评估了50例患者的rhoA和rhoC mRNA水平。
ESCC细胞系中的rhoA和rhoC高于非癌性食管细胞。rhoC在TTn中过表达，TTn直接取自下颌骨ESCC转移灶的手术标本。ESCC患者的rhoA和rhoC显著高于正常对照（分别为P = 0.0022和P < 0.0001）。rhoA与肿瘤分化相关，rhoC与肿瘤进展、淋巴结转移系统分类相关。ESCC中的rhoA和rhoC呈正相关（P = 0.008）。rhoA过表达的患者预后明显比rhoA低表达的患者差（P = 0.044）。
据我们所知，本研究首次检测并比较了ESCC中RhoA和RhoC在mRNA水平的表达与其正常对照的情况。我们的数据表明rhoA和rhoC参与ESCC进展，可作为预后标志物。需要进一步研究检查Rho GTP酶抑制剂作为一种有前景的抗癌疗法，尤其是在ESCC中的治疗潜力。
