title: The role of PKR/eIF2α signaling pathway in prognosis of non-small cell lung cancer.
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).
  
  
  RESULTS
  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.
authors.affiliation: Department of Thoracic Surgery, Daping Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: He
authors.forename: Arlene M
authors.initials: AM
authors.lastname: Correa
authors.forename: Maria Gabriela
authors.initials: MG
authors.lastname: Raso
authors.forename: Wayne L
authors.initials: WL
authors.lastname: Hofstetter
authors.forename: Bingliang
authors.initials: B
authors.lastname: Fang
authors.forename: Carmen
authors.initials: C
authors.lastname: Behrens
authors.forename: Jack A
authors.initials: JA
authors.lastname: Roth
authors.forename: Yihong
authors.initials: Y
authors.lastname: Zhou
authors.forename: Liping
authors.initials: L
authors.lastname: Yu
authors.forename: Ignacio I
authors.initials: II
authors.lastname: Wistuba
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Swisher
authors.forename: Apar
authors.initials: A
authors.lastname: Pataer
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism* / Q000401:mortality; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D015852:Eukaryotic Initiation Factor-2 / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000401:mortality; D008297:Male; D010766:Phosphorylation; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D015996:Survival Rate; D019892:eIF-2 Kinase / Q000235:genetics* / Q000378:metabolism*
chemical_list: D015852:Eukaryotic Initiation Factor-2; D012333:RNA, Messenger; D019892:eIF-2 Kinase
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