Activation of P21-activated protein kinase 2 is an independent prognostic predictor for patients with gastric cancer.
Activation of P21-activated protein kinase 2 is an independent prognostic predictor for patients with gastric cancer.
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DOI：
10.1186/1746-1596-9-55
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发表时间：
2014-03-12
影响因子：
2.6
通讯作者：
Xie R
中科院分区：
文献类型：
--
作者：
Gao C;Ma T;Pang L;Xie R
p21激活激酶（p21-activated kinase，PAK）2是PAK家族激酶中的一员，参与细胞增殖、存活、有丝分裂、凋亡、运动和血管生成等过程。然而，PAK 2在人胃癌中的激活的临床意义尚未完全阐明。本研究旨在探讨PAK 2表达及其磷酸化状态与胃癌进展及预后的关系。应用免疫组织化学方法检测82例胃癌组织中PAK 2和丝氨酸20磷酸化PAK 2（pSer 20 PAK 2）的表达及亚细胞定位。PAK 2和pSer 20 PAK 2免疫组化染色均定位于胃癌组织肿瘤细胞的胞浆内。与正常胃粘膜相比，PAK 2和pSer 20 PAK 2蛋白的表达水平均明显升高（均P < 0.001）。此外，PAK 2和pSer 20 PAK 2蛋白过度表达的患者与不利的临床病理变量显著相关，包括较高的肿瘤深度（P值分别为0.022和0.036），淋巴结转移程度越大（P分别为0.022和0.036）、远处转移（P分别为0.025和0.038）和晚期肿瘤（P分别为0.018和0.031）。此外，过表达PAK 2和pSer 20 PAK 2蛋白的患者相对于没有这些蛋白过表达的患者具有较差的总体存活率。考克斯多因素分析显示PAK 2（p = 0.012）和pSer 20 PAK 2（p = 0.010）是胃癌的独立预后因素。我们的数据首次表明PAK 2激活可能与胃癌的晚期肿瘤进展和不良预后相关。本文的虚拟幻灯片可以在这里找到：http://www.diagnosticpathology.diagnomx.eu/vs/1236344107120406。
p21-activated kinase (PAK) 2, as a member of the PAK family kinases, is involved in a number of hallmark processes including cell proliferation, survival, mitosis, apoptosis, motility and angiogenesis. However, the clinical significance of the activation of PAK2 in human gastric cancer has not been fully elucidated. The aim of this study was to investigate whether PAK2 expression and its phosphorylation status are correlated with tumor progression and prognosis in gastric cancer. Expression patterns and subcellular localizations of PAK2 and Ser20-phosphorylated PAK2 (pSer20PAK2) in 82 gastric cancer patients were detected by immunohistochemistry. Both PAK2 and pSer20PAK2 immunostainings were localized in the cytoplasm of tumor cells of gastric cancer tissues. Compared with the normal gastric mucosa, the expression levels of PAK2 and pSer20PAK2 proteins were both significantly increased (both P < 0.001). Additionally, the patients displaying the over-expression of PAK2 and pSer20PAK2 proteins were dramatically associated with unfavorable clinicopathologic variables including higher tumor depth (P = 0.022 and 0.036, respectively), greater extent of lymph node metastasis ((P = 0.022 and 0.036, respectively), positive distant metastasis (P = 0.025 and 0.038, respectively) and advanced tumor stage (P = 0.018 and 0.031, respectively). Moreover, the patients overexpressing PAK2 and pSer20PAK2 proteins have poor overall survival rates relative to those without overexpression of these proteins. Furthermore, cox multi-factor analysis showed that PAK2 (p = 0.012) and pSer20PAK2 (p = 0.010) were independent prognosis factors for human gastric cancer. Our data suggest for the first time that PAK2 activation may be associated with advanced tumor progression and poor prognosis of gastric cancer. The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1236344107120406.
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