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

Clinical and prognostic significance of RhoA and RhoC gene expression in esophageal squamous cell carcinoma
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DOI:
10.1245/s10434-007-9562-x
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发表时间:
2007-12-01
影响因子:
3.7
通讯作者:
Kuwano, Hiroyuki
Kuwano, Hiroyuki
中科院分区:
医学2区
文献类型:
--
作者:
Faried, Ahmad;Faried, Leri S.;Kuwano, Hiroyuki

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背景:Rho GTP酶参与微丝网络的组织、细胞间相互作用和恶性转化。为探讨Rho GTPases在食管鳞状细胞癌(ESCC)中的作用,本研究采用实时荧光定量RT-PCR技术,检测食管鳞癌组织和正常食管组织中RhoA和RhoC的mRNA水平。结果:食管鳞癌细胞系中rhoA和rhoC的mRNA水平明显高于正常食管上皮细胞。rhoC在TTn中过表达,TTn直接从下颌骨ESCC转移灶的手术标本中获得。食管鳞癌患者的rhoA和rhoC显著高于正常对照组(分别为P = 0.0022和P <0.0001)。rhoA与肿瘤分化相关,rhoC与晚期肿瘤、淋巴结、转移系统分类相关。食管鳞癌中rhoA和rhoC呈正相关(P = 0.008)。rhoA过度表达的患者的预后明显差于rhoA低表达的患者(P = 0.044)。结论:据我们所知,本研究首次在食管鳞癌中检测了RhoA和RhoC在mRNA水平上的表达,并与正常对照组进行了比较。我们的研究结果表明rhoA和rhoC参与了ESCC的进展,并可作为预后标志物。将需要进一步的研究来检查Rho GTdR抑制剂作为有希望的抗癌疗法的治疗潜力,特别是在ESCC中。
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.