The downregulation of Rap1 GTPase-activating protein is associated with a poor prognosis in colorectal cancer and may impact on tumor progression.
The downregulation of Rap1 GTPase-activating protein is associated with a poor prognosis in colorectal cancer and may impact on tumor progression.
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DOI：
10.3892/ol.2018.8305
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发表时间：
2018-05
期刊：
影响因子：
2.9
通讯作者：
Wei L
中科院分区：
文献类型：
--
作者：
Gao WL;Ye GC;Liu LW;Wei L
Rap 1 GTP酶激活蛋白（Rap 1GAP）作为Rap 1活性的负调节因子，通过特异性刺激在多种癌症中发挥重要作用。然而，Rap 1GAP在结直肠癌（CRC）中的作用尚未完全阐明。本研究旨在探讨Rap 1GAP在大肠癌组织中的表达及其临床意义。采用免疫组化法检测227例大肠癌组织及癌旁组织中Rap 1GAP、基质金属肽酶9（MMP-9）和E-cadherin的表达。研究Rap 1GAP表达与结直肠癌临床病理特征及预后（OS + DFS）的关系。此外，还研究了Rap 1GAP表达与MMP-9表达之间的关系，以及Rap 1GAP表达与E-cadherin表达之间的关系。Rap 1GAP在大肠癌组织中的表达明显低于癌旁组织。Rap 1GAP表达降低与结直肠癌患者手术后浸润深度、淋巴结转移、肿瘤转移分期及预后不良显著相关。此外，单变量和多变量分析显示Rap 1GAP是无病生存期和总生存期的独立不良预后因素。此外，Rap 1GAP表达与MMP-9呈负相关，与E-cadherin呈正相关。总之，本研究的结果表明Rap 1GAP可能参与了CRC的肿瘤进展，并可能作为CRC患者预后预测的潜在靶点。
Rap1 GTPase-activating protein (Rap1GAP) has been reported to serve an important role in various types of cancer by specific stimulation as a negative regulator of Rap1 activity. However, the role of Rap1GAP in colorectal cancer (CRC) has yet to be fully elucidated. The aim of the present study was to investigate the expression of Rap1GAP in CRC tissues and to elucidate its clinical significance. The expression of Rap1GAP, matrix metallopeptidase 9 (MMP-9) and E-cadherin in 227 CRC tissues and paired para-carcinoma tissues was detected by immunohistochemistry. Associations between Rap1GAP expression and clinicopathological characteristics, and between Rap1GAP expression and prognostic value (OS + DFS) in CRC were investigated. Furthermore, associations between Rap1GAP expression and MMP-9 expression, and between Rap1GAP expression and E-cadherin expression were also investigated. Rap1GAP expression was markedly downregulated in CRC tissues compared with para-carcinoma tissues. Decreased expression of Rap1GAP was significantly associated with depth of invasion, lymph node metastasis, advanced Tumor-Node-Metastasis stage and a poor prognosis in patients with CRC following surgery. Furthermore, univariate and multivariate analyses revealed that Rap1GAP was an independent poor prognostic factor for disease-free survival and overall survival. In addition, Rap1GAP expression was negatively associated with MMP-9 and positively associated with E-cadherin in 227 CRC samples. In brief, the results of the present study suggested that Rap1GAP may be involved in tumor progression in CRC and may serve as a potential target for prognostic prediction of patients with CRC.
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影响因子：
11.2
作者：
Onder, Tamer T.;Gupta, Piyush B.;Weinberg, Robert A.
通讯作者：
Weinberg, Robert A.
影响因子：
24.5
作者：
Hur K;Toiyama Y;Takahashi M;Balaguer F;Nagasaka T;Koike J;Hemmi H;Koi M;Boland CR;Goel A
通讯作者：
Goel A
基质金属蛋白酶及其在结直肠癌中的抑制剂的行为。
影响因子：
5.6
作者：
Herszényi L;Hritz I;Lakatos G;Varga MZ;Tulassay Z
通讯作者：
Tulassay Z
影响因子：
11.2
作者：
Bailey CL;Kelly P;Casey PJ
通讯作者：
Casey PJ
影响因子：
2.7
作者：
Brabletz, T;Hlubek, F;Kirchner, T
通讯作者：
Kirchner, T