Prognostic significance of combinations of RNA-dependent protein kinase and EphA2 biomarkers for NSCLC.
Prognostic significance of combinations of RNA-dependent protein kinase and EphA2 biomarkers for NSCLC.
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DOI：
10.1097/jto.0b013e318282def7
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发表时间：
2013-03
期刊：
影响因子：
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通讯作者：
Pataer A
中科院分区：
文献类型：
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作者：
Guo C;Shao R;Correa AM;Behrens C;Johnson FM;Raso MG;Prudkin L;Solis LM;Nunez MI;Fang B;Roth JA;Wistuba II;Swisher SG;Lin T;Pataer A
rna依赖性蛋白激酶（PKR）是非小细胞肺癌（NSCLC）患者的独立预后变量。在本研究中，我们研究了PKR与其他25个NSCLC生物标志物的相关性，确定了能够进一步提高PKR预后意义的标志物，并阐明了这些标志物与PKR相互作用的机制。从218名肺癌患者中获得的组织微阵列样本用抗pkr抗体和针对25种生物标志物的抗体进行染色。免疫组织化学表达评分并用于Kaplan-Meier生存分析。研究了PKR与EphA2在非小细胞肺癌细胞系中的相互作用。我们发现PKR与EphA2相关，PKR和EphA2联合提供的非小细胞肺癌预后信息（P/E）明显比单独使用任何一种标志物更准确。PKRlow/EphA2high患者的5年总生存率（20%）显著低于PKRhigh/EphA2low患者（74%）、PKRhigh/EphA2high患者（55%）和PKRlow/EphA2low患者（55%）（p< 0.0001）。我们还发现PKR:EphA2 （P/E）比值与预后显著相关（P < 0.0001）。单因素和多因素Cox分析显示，该P/E组合或比率是总生存率的独立预测因子。此外，诱导PKR表达降低了EphA2蛋白在NSCLC细胞系中的表达水平。PKR/EphA2是NSCLC预后的重要预测因子。PKR/EphA2可能是提高NSCLC患者筛查效率和预测预后的一种有前景的方法。
RNA-dependent protein kinase (PKR) is an independent prognostic variable in patients with non-small cell lung cancer (NSCLC). In the present study, we investigated the correlation between PKR and 25 other biomarkers for NSCLC, identified the markers that could further improve the prognostic significance of PKR, and elucidated the mechanisms of interaction between these markers and PKR. Tissue microarray samples obtained from 218 lung cancer patients were stained with an anti-PKR antibody and antibodies against 25 biomarkers. Immunohistochemical expression was scored and used for Kaplan-Meier survival analysis. The interaction between PKR and EphA2 in NSCLC cell lines was examined. We found that PKR was associated with EphA2 and that the prognostic information regarding NSCLC provided by the combination of PKR and EphA2 (P/E) was significantly more accurate than that provided by either marker alone. The 5-year overall survival rate in PKRlow/EphA2high patients (20%) was significantly lower than that of PKRhigh/EphA2low patients (74%), PKRhigh/EphA2high patients (55%), and PKRlow/EphA2low patients (55%) (p< 0.0001). We also found that the PKR:EphA2 (P/E) ratio was significantly associated with prognosis (p< 0.0001). Univariate and multivariate Cox analyses revealed that this P/E combination or ratio was an independent predictor of overall survival. In addition, induction of PKR expression reduced EphA2 protein expression levels in NSCLC cell lines. PKR/EphA2 is a significant predictor of prognosis for NSCLC. PKR/EphA2 may be a promising approach to improving screening efficiency and predicting prognosis in NSCLC patients.