Overexpression of protein phosphatase 4 correlates with poor prognosis in patients with stage II pancreatic ductal adenocarcinoma.
Overexpression of protein phosphatase 4 correlates with poor prognosis in patients with stage II pancreatic ductal adenocarcinoma.
复制标题
DOI：
10.1158/1055-9965.epi-12-0223
复制
发表时间：
2012-08
期刊：
影响因子：
--
通讯作者：
Wang H
中科院分区：
文献类型：
--
作者：
Weng S;Wang H;Chen W;Katz MH;Chatterjee D;Lee JE;Pisters PW;Gomez HF;Abbruzzese JL;Fleming JB;Wang H
蛋白磷酸酶4(PP4)已被报道在乳腺癌和肺癌中过表达。PP4在中心体成熟、DNA修复、核因子κB和JNK信号通路中起着重要的调节作用。然而，PP4在胰腺癌中的表达和功能尚未见报道。应用免疫组织化学(IHC)法检测133例II期胰腺导管腺癌(PDAC)及其配对的良性胰腺组织(N=113)中PP4催化亚单位(PP4C)的表达。为了证实免疫组化的结果，我们用Western blotting和Real Time RT-PCR检测了PP4C蛋白和mRNA的水平。使用单因素和多因素分析，我们将PP4C的表达与生存期和其他临床病理特征相关联。PP4C在133例II期胰腺癌组织中有75例(56.4%)过表达，显著高于配对的良性胰腺组织(15%，17/113)。PDAC组织中PP4C基因的表达水平也高于配对的良性胰腺组织。与肿瘤大小、切缘状态和淋巴结状态(分期)无关的II期患者的远处转移率较高(p=0.006.0 2)，无瘤生存率和总生存率较低(p=0.0 2)。我们的研究表明，PP4C在PDAC中过表达。PP4C在PDAC样本中的过度表达与II期PDAC患者的预后不良有关。因此，靶向PP4信号通路可能成为治疗PDAC的新途径。我们的研究表明，PP4C是II期PDAC患者的一个独立预后因素。
Protein phosphatase 4 (PP4) has been reported to be overexpressed in breast and lung cancers. PP4 plays an important role in the regulation of centrosome maturation, DNA repair, NFκB and JNK signaling pathways. However, the expression and functions of PP4 in pancreatic cancer have not been studied. We examined the expression of PP4 catalytic subunit (PP4C) protein in 133 patients with stage II pancreatic ductal adenocarcinoma (PDAC) and their paired benign pancreatic samples (N=113) by immunohistochemistry (IHC). To confirm the IHC results, we measured PP4C protein and mRNA levels by Western blotting and real time RT-PCR. Using univariate and multivariate analysis, we correlated PP4C expression with survival and other clinicopathologic features. PP4C was overexpressed in 75 of 133 (56.4%) stage II PDAC samples, which was significantly higher than the paired benign pancreatic tissue (15%, 17/113). PP4C mRNA expression levels were also higher in PDAC samples than the paired benign pancreatic tissue. Overexpression of PP4C in PDAC samples was associated with higher frequencies of distant metastasis (p=0.02) and poor disease-free and overall survivals in patients with stage II PDAC (p = 0.006 and 0.02) independent of tumor size, margin status, and lymph node status (stage). Our study showed that PP4C is overexpressed in PDAC. Overexpression of PP4C in PDAC samples is associated with poor prognosis in patients with stage II PDAC. Therefore, targeting PP4 signaling pathway may represent a new approach for the treatment of PDAC. Our study demonstrated that PP4C is an independent prognostic factor in patients with stage II PDAC.