The Role of PKR/eIF2α Signaling Pathway in Prognosis of Non-Small Cell Lung Cancer

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 alpha (p-eIF2 alpha). Methodology and Findings: 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 alpha 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 alpha expression had a significantly longer median survival than those with little or no p-PKR or p-eIF2 alpha 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 alpha 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 alpha can be new markers for predicting the prognosis of patients with NSCLC.