DAPK1 as an independent prognostic marker in liver cancer.
DAPK1 as an independent prognostic marker in liver cancer.
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DAPK1 作为肝癌的独立预后标志物。
作者：
Li L;Guo L;Wang Q;Liu X;Zeng Y;Wen Q;Zhang S;Kwok HF;Lin Y;Liu J
死亡相关蛋白激酶1 （DAPK1）可以作为癌基因或肿瘤抑制基因，这取决于细胞环境和外部刺激。我们的研究旨在从mRNA和蛋白水平探讨DAPK1在肝癌中的预后意义。在三个独立的肝癌数据库中提取DAPK1的mRNA表达，并在我们的中国肝癌患者队列中通过免疫组织化学检测DAPK1的蛋白表达。检测DAPK1表达与临床特征之间的关系。肝癌组织中DAPK1 mRNA表达下调。在肝癌患者队列中，低水平的DAPK1 mRNA与较短的生存期相关（n = 115; p = 0.041），而DAPK1蛋白阴性染色与较短的进展时间（p = 0.002）和总生存期（p = 0.02）显著相关。通过多变量分析，DAPK1是进展时间和总生存期的独立预后标志物。发生b-catenin突变的肝癌患者DAPK1表达水平较低，提示DAPK1可能在b-catenin通路下受到调控。此外，我们还鉴定了与DAPK1共调控的基因。在两个肝癌数据集中，DAPK1的表达与IRF2、IL7R、PCOLCE和ZBTB16呈正相关，与SLC16A3呈负相关。其中PCOLCE和ZBTB16在肝癌中显著下调，SLC16A3在肝癌中显著上调。通过使用这些共调控基因的连接图谱，我们已经确定氨酰胺和舒必利是潜在的小分子，可以潜在地逆转DAPK1/PCOLCE/ZBTB16/SLC16A3的表达。我们的研究首次证明了DAPK1 mRNA和蛋白表达水平是肝癌的重要预后指标，并鉴定了可能参与DAPK1介导的肝癌发生的基因。
The death-associated protein kinase 1 (DAPK1) can act as an oncogene or a tumor suppressor gene depending on the cellular context as well as external stimuli. Our study aims to investigate the prognostic significance of DAPK1 in liver cancer in both mRNA and protein levels. The mRNA expression of DAPK1 was extracted from the Gene Expression Omnibus database in three independent liver cancer datasets while protein expression of DAPK1 was detected by immunohistochemistry in our Chinese liver cancer patient cohort. The associations between DAPK1 expression and clinical characteristics were tested. DAPK1 mRNA expression was down-regulated in liver cancer. Low levels of DAPK1 mRNA were associated with shorter survival in a liver cancer patient cohort (n = 115; p = 0.041), while negative staining of DAPK1 protein was significantly correlated with shorter time to progression (p = 0.002) and overall survival (p = 0.02). DAPK1 was an independent prognostic marker for both time to progression and overall survival by multivariate analysis. Liver cancer with the b-catenin mutation has a lower DAPK1 expression, suggesting that DAPK1 may be regulated under the b-catenin pathway. In addition, we also identified genes that are co-regulated with DAPK1. DAPK1 expression was positively correlated with IRF2, IL7R, PCOLCE and ZBTB16, and negatively correlated with SLC16A3 in both liver cancer datasets. Among these genes, PCOLCE and ZBTB16 were significantly down-regulated, while SLC16A3 was significantly upregulated in liver cancer. By using connectivity mapping of these co-regulated genes, we have identified amcinonide and sulpiride as potential small molecules that could potentially reverse DAPK1/PCOLCE/ZBTB16/SLC16A3 expression. Our study demonstrated for the first time that both DAPK1 mRNA and protein expression levels are important prognostic markers in liver cancer, and have identified genes that may contribute to DAPK1-mediated liver carcinogenesis.
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影响因子：
16
作者：
Lee TH;Chen CH;Suizu F;Huang P;Schiene-Fischer C;Daum S;Zhang YJ;Goate A;Chen RH;Zhou XZ;Lu KP
通讯作者：
Lu KP
CDK5和p27的低表达与胃癌患者的不良预后相关
影响因子：
3.9
作者：
Sun YQ;Xie JW;Chen PC;Zheng CH;Li P;Wang JB;Lin JX;Lu J;Chen QY;Cao LL;Lin M;Tu RH;Lin Y;Huang CM
通讯作者：
Huang CM
影响因子：
11.2
作者：
Mokkapati S;Niopek K;Huang L;Cunniff KJ;Ruteshouser EC;deCaestecker M;Finegold MJ;Huff V
通讯作者：
Huff V
影响因子：
3.7
作者：
McArt DG;Zhang SD
通讯作者：
Zhang SD
影响因子：
30.8
作者：
Sung, Wing-Kin;Zheng, Hancheng;Luk, John M.
通讯作者：
Luk, John M.