Abstract 2250: PKR signaling pathway plays an important role in prognosis for non-small cell lung cancer

Abstract

Abstract The role of RNA-dependent protein kinase (PKR) in antiviral defence 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 PKR's expression in tissue microarray specimens from both non-small cell lung cancer (NSCLC) and normal human bronchial epithelium tissue. 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 that PKR to be a powerful prognostic factor in TMA-2 lung cancer (HR=0.22, P<0.0001). We also observed that the patients with high p-PKR or p-eIF2a expression had a significantly longer median survival than those with little or no p-PKR or p-eIF2a expression (P = 0.03 and P = 0.032, respectively). Combined expression of PKR and p-PKR or PKR and p-eIF2a increased patient survival (P = 0.001). Combined expression levels of PKR and p-PKR or p-eIF2a can be new markers for predicting the prognosis of patients with NSCLC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2250. doi:10.1158/1538-7445.AM2011-2250