Prognostic importance and therapeutic implications of PAK1, a drugable protein kinase, in gastroesophageal junction adenocarcinoma.
Prognostic importance and therapeutic implications of PAK1, a drugable protein kinase, in gastroesophageal junction adenocarcinoma.
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PAK1（一种药物蛋白激酶）在胃食管结合部腺癌中的预后重要性和治疗意义
DOI：
10.1371/journal.pone.0080665
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Zhang H
中科院分区：
文献类型：
--
作者：
Li Z;Zou X;Xie L;Dong H;Chen Y;Liu Q;Wu X;Zhou D;Tan D;Zhang H
胃食管交界处（GEJ）腺癌是一种发病率不断上升的致死性癌症，然而具有强烈预后影响和具有巨大治疗前景的分子生物标志物仍然难以捉摸。我们使用数据挖掘方法确定了p21蛋白活化激酶1 (PAK1)，一种致癌基因和可药物蛋白激酶，是GEJ腺癌最有希望的靶点之一。免疫印迹分析和数据挖掘表明，与非癌组织相比，PAK1蛋白和mRNA在癌组织中表达上调。免疫组化显示PAK1在原发性GEJ腺癌中过表达72.6% （n = 113）。从成对的正常上皮到非典型增生和腺癌，PAK1水平呈逐步增加的趋势。PAK1在肿瘤中的过表达与淋巴结（LN）转移（P<0.001）、肿瘤分期晚期（P<0.001）、肿瘤大小较大（P = 0.006）、手术切缘残留（P = 0.033）和不利的总生存期（P<0.001）相关。多因素分析显示PAK1过表达是独立的高危预后预测因子（P<0.001）。总的来说，PAK1在肿瘤发生过程中过度表达，其上调与主要与侵袭和转移相关的恶性特性相关。PAK1表达可作为GEJ腺癌的预后预测因子，具有治疗前景。
Gastroesophageal junction (GEJ) adenocarcinoma is a lethal cancer with rising incidence, yet the molecular biomarkers that have strong prognostic impact and also hold great therapeutic promise remain elusive. We used a data mining approach and identified the p21 protein-activated kinase 1 (PAK1), an oncogene and drugable protein kinase, to be among the most promising targets for GEJ adenocarcinoma. Immunoblot analysis and data mining demonstrated that PAK1 protein and mRNA were upregulated in cancer tissues compared to the noncancerous tissues. Immunohistochemistry revealed PAK1 overexpression in 72.6% of primary GEJ adenocarcinomas (n = 113). A step-wise increase in PAK1 levels was noted from paired normal epithelium, to atypical hyperplasia and adenocarcinoma. PAK1 overexpression in tumor was associated with lymph node (LN) metastasis (P<0.001), advanced tumor stage (P<0.001), large tumor size (P = 0.006), residual surgical margin (P = 0.033), and unfavorable overall survival (P<0.001). Multivariate analysis showed PAK1 overexpression is an independent high-risk prognostic predictor (P<0.001). Collectively, PAK1 is overexpressed during tumorigenic progression and its upregulation correlates with malignant properties mainly relevant to invasion and metastasis. PAK1 expression could serve as a prognostic predictor that holds therapeutic promise for GEJ adenocarcinoma.
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DOI：
10.1158/1078-0432.ccr-11-1952
发表时间：
2012-07-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Eswaran J;Li DQ;Shah A;Kumar R
通讯作者：
Kumar R
影响因子：
5.8
作者：
Bain, Gillian H.;Petty, Russell D.
通讯作者：
Petty, Russell D.
DOI：
10.1073/pnas.191389398
发表时间：
2001-09-25
影响因子：
11.1
作者：
Gaxiola, RA;Li, JS;Fink, GR
通讯作者：
Fink, GR
影响因子：
3.7
作者：
Hasegawa, Shinichi;Yoshikawa, Takaki;Tsuburaya, Akira
通讯作者：
Tsuburaya, Akira
影响因子：
11.5
作者：
Bostner, Josefine;Skoog, Lambert;Stal, Olle
通讯作者：
Stal, Olle