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- Title
The Role of PKR/eIF2α Signaling Pathway in Prognosis of Non-Small Cell Lung Cancer.
- Authors
He, Yong; Correa, Arlene M.; Raso, Maria Gabriela; Hofstetter, Wayne L.; Fang, Bingliang; Behrens, Carmen; Roth, Jack A.; Zhou, Yihong; Yu, Liping; Wistuba, Ignacio I.; Swisher, Stephen G.; Pataer, Apar
- Abstract
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 eIF2α (p-eIF2α). 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-eIF2α 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-eIF2α expression had a significantly longer median survival than those with little or no p-PKR or p-eIF2α 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-eIF2α 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-eIF2α can be new markers for predicting the prognosis of patients with NSCLC.
- Subjects
PROGNOSIS; LUNG cancer; MESSENGER RNA; BIOMARKERS; WESTERN immunoblotting
- Publication
PLoS ONE, 2011, Vol 6, Issue 11, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0024855