Prognostic Significance of RNA-Dependent Protein Kinase on Non-Small Cell Lung Cancer Patients
Prognostic Significance of RNA-Dependent Protein Kinase on Non-Small Cell Lung Cancer Patients
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DOI：
10.1158/1078-0432.ccr-10-0753
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发表时间：
2010-11-15
影响因子：
11.5
通讯作者：
Swisher, Stephen G.
中科院分区：
文献类型：
--
作者：
Pataer, Abujiang;Raso, Maria Gabriela;Swisher, Stephen G.
目的：RNA依赖蛋白激酶(PKR)在抗病毒防御机制以及细胞分化、生长和凋亡中的作用已为人们所熟知，但对其在人类肺癌中的作用仍知之甚少。为了探讨PKR在人类肺癌中的作用，我们检测了非小细胞肺癌(NSCLC)和正常支气管上皮组织微阵列(TMA)标本中PKR的表达。实验设计：用PKR抗体对231例肺癌TMA标本(TMA-1)进行染色，并对224例肺癌TMA-2进行验证。免疫组织化学评分由三位病理学家独立进行量化。用Kaplan-Meier法计算存活概率。结果：NSCLC细胞的PKR表达水平低于正常支气管上皮细胞。我们还发现低水平的PKR表达与淋巴转移显著相关。我们发现，PKR表达缺失与更具攻击性的行为相关，并且PKR高表达预示着一组预后良好的患者。单因素和多因素COX比例风险回归模型显示，PKR表达水平低与NSCLC患者的生存期缩短显著相关。我们进一步验证和确认了PKR是TMA-2肺癌的一个强有力的预后因素(风险比，0.22；P<；0.0001)。结论：我们的发现首次表明PKR的表达是非小细胞肺癌患者的一个独立的预后变量。临床癌症资源；16(22)；5522-8。(C)2010年AACR。
Purpose: The role of RNA-dependent protein kinase (PKR) in antiviral defense mechanisms and in cellular differentiation, growth, and apoptosis is well known, but the role of PKR in human lung cancer remains poorly understood. To explore the role of PKR in human lung cancer, we evaluated the expression of PKR in tissue microarray (TMA) specimens from both non-small cell lung cancer (NSCLC) and normal human bronchial epithelium tissue.Experimental Design: TMA samples (TMA-1) from 231 lung cancers were stained with PKR antibody and validated on TMA-2 from 224 lung cancers. Immunohistochemical expression score was quantified by three pathologists independently. Survival probability was computed by the Kaplan-Meier method.Results: The NSCLC cells showed lower levels of PKR expression than normal bronchial epithelium cells did. We also found a significant association between lower levels of PKR expression and lymph node metastasis. We found that loss of PKR expression is correlated with a more aggressive behavior, and that a high PKR expression predicts a subgroup of patients with a favorable outcome. Univariate and multivariate Cox proportional hazards regression models showed that a lower level of PKR expression was significantly associated with shorter survival in NSCLC patients. We further validated and confirmed PKR to be a powerful prognostic factor in TMA-2 lung cancer (hazard ratio, 0.22; P < 0.0001).Conclusions: Our findings first indicate that PKR expression is an independent prognostic variable in NSCLC patients. Clin Cancer Res; 16(22); 5522-8. (C) 2010 AACR.