The Role of PKR/eIF2 alpha Signaling Pathway in Prognosis of Non-Small Cell Lung Cancer

The Role of PKR/eIF2 alpha Signaling Pathway in Prognosis of Non-Small Cell Lung Cancer
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PKR/eIF2 α信号通路在非小细胞肺癌预后中的作用

DOI:
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发表时间:
2011
期刊:
影响因子:
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通讯作者:
Pataer
Pataer
中科院分区:
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文献类型:
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作者:
Yong He;A. Correa;M. G. Raso;W. Hofstetter;B. Fang;Carmen;Behrens;J. Roth;Yihong Zhou;Liping Yu;I. Wistuba;S. Swisher;Apar;Pataer

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背景资料:在这项研究中,我们研究了PKR蛋白表达是否与mRNA水平相关,并评估了与PKR相关的分子生物标志物,如磷酸化PKR(p-PKR)和磷酸化eIF 2 a(p-eIF 2 a)。方法和结果:采用Western blot和实时荧光定量RT-PCR方法检测36例新鲜肺肿瘤组织中PKR蛋白和mRNA的表达水平。我们使用组织微阵列对p-PKR和p-eIF 2a蛋白的表达进行免疫组织化学评价。我们证明PKR mRNA水平与PKR蛋白水平显著相关(斯皮尔曼rho = 0.55,p,0.001),表明肿瘤样品中PKR蛋白水平受PKR mRNA调节。我们还观察到p-PKR或p-eIF 2 a高表达的患者比p-PKR或p-eIF 2 a表达很少或没有表达的患者具有显著更长的中位生存期(分别为p =0.03和p = 0.032)。我们进一步评估了p-PKR加PKR和p-eIF 2 α加PKR的组合表达的预后效果,发现两种组合都是I期和所有期患者总体患者生存的强独立预后标志物。结论:PKR蛋白表达可能受转录水平的调控。PKR与p-PKR或p-eIF 2 α的联合表达水平可作为预测NSCLC患者预后的新指标。(to SS)。资助者在研究设计、数据收集和分析、决定或准备
Background: In this study, we investigated whether PKR protein expression is correlated with mRNA levels and also evaluated molecular biomarkers that are associated with PKR, such as phosphorylated PKR (p-PKR) and phosphorylated eIF2 a (p-eIF2 a ). MethodologyandFindings: We determined the levels of PKR protein expression and mRNA in 36 fresh primary lung tumor tissues by using Western blot analysis and real-time reverse-transcriptase PCR (RT-PCR), respectively. We used tissue microarrays for immunohistochemical evaluation of the expression of p-PKR and p-eIF2 a proteins. We demonstrated that PKR mRNA levels are significantly correlated with PKR protein levels (Spearman’s rho = 0.55, p , 0.001), suggesting that PKR protein levels in tumor samples are regulated by PKR mRNA. We also observed that the patients with high p-PKR or p-eIF2 a expression had a significantly longer median survival than those with little or no p-PKR or p-eIF2 a expression ( p =0.03 and p = 0.032, respectively). We further evaluated the prognostic effect of combined expression of p-PKR plus PKR and p-eIF2 a plus PKR and found that both combinations were strong independent prognostic markers for overall patient survival on stage I and all stage patients. Conclusions: Our findings suggest that PKR protein expression may controlled by transcription level. Combined expression levels of PKR and p-PKR or p-eIF2 a can be new markers for predicting the prognosis of patients with NSCLC. (to SS). The funders had no role in study design, data collection and analysis, decision to or preparation of the
DOI: 10.1158/0008-5472.can-08-3858
发表时间: 2009-02-15
期刊: Cancer research
影响因子: 11.2
作者:
Schewe DM;Aguirre-Ghiso JA
通讯作者: Aguirre-Ghiso JA