肝癌细胞转移与PI3K-Akt-PAK1通路的相关性研究

Expression of P I3K-Akt-P AK1 pathway in the process of m etastasis of hepatocellular carcinoma

目的研究肝细胞癌(HCC)组织PI3K/Akt/p21活化蛋白激酶1(PAK1)信号通路的表达对于HCC发生及转移的重要性,以期为HCC的预防和预后提供一个有效的分子标志,并为HCC的治疗提供一定的理论基础。方法自NCBI中GEO数据库中的GES364数据集提取数据,对PI3K/Akt/PAK1信号通路基因的表达量进行分析。结果将数据库中HCC组织分为肝内扩散组(PS)、肝外转移组(PM)、无转移组(PN)和正常肝对照组(H)。分析发现PS组和PM组PAK1和MMP-9表达量明显高于H组和PN组(P<0.0001);PS组、PM组和PN组AKT(1/2)和Girdin表达量明显高于H组(P<0.05),PS组和PM组AKT2和Girdin表达量也明显高于PN组(P<0.05);在PM组,AKT2与PAK1表达呈正相关(r=0.5679,P=0.0013)。结论 PAK1和MMP-9高表达可以促进HCC的扩散和转移,而AKT的表达和活性对于HCC的转移也是至关重要的,提示PI3K/AKT/PAK1信号通路与HCC转移密切相关。

Objective Based on relevant database data,we tried to explore the importance of PI3K/Akt/PAK1 signaling pathway to HCC metastasis and provide an effective molecular marker for the prevention of HCC. Methods From GES364 data sets of GEO in the NCBI database,we searched the materials about the PI3K/Akt/PAK1 expression in intrahepatic spread （IHS）,entrahepatic metastasis （EHM）,non-metastasis （NM） and normal livers （N）. Results The expression of PAK1 and MMP-9 were up-regulated in IHS and EHM group（P〈0.0001） as compared with those in normal liver and NM group; the expression of AKT （1/2） and Girdin were up-regulated in the IHS,EHM and NM group （P〈0.05） as compared with in normal liver;in the EHM group,the expression of AKT2 was positively correlated to PAKI （r=0.5679,P=0.0013）. Conclusions The up-regulation of PAK1 and MMP-9 could promote the spread and metastasis of HCC cells,the increased expression and activities of AKT are crucial for metastasis of liver cancer,and the PI3K/AKT/PAK1 signaling pathway is closely related to the development and metastasis in patients with HCC.