Prognostic significance of combinations of RNA-dependent protein kinase and EphA2 biomarkers for NSCLC.
BACKGROUND
RNA-dependent protein kinase (PKR) is an independent prognostic variable in patients with non-small-cell lung cancer (NSCLC). In the current study, we investigated the correlation between PKR and 25 other biomarkers for NSCLC, identified the markers that could further improve the prognostic significance of PKR and elucidated the mechanisms of interaction between these markers and PKR.


METHODS
Tissue microarray samples obtained from 218 patients with lung cancer were stained with an anti-PKR antibody and antibodies against 25 biomarkers. Immunohistochemical expression was scored and used for Kaplan-Meier survival analysis. The interaction between PKR and EphA2 in NSCLC cell lines was examined.


RESULTS
We found that PKR was associated with EphA2 and that the prognostic information regarding NSCLC provided by the combination of PKR and EphA2 (P/E) was significantly more accurate than that provided by either marker alone. The 5-year overall survival rate in patients with PKR/EphA2 (20%) was significantly lower than that of patients with PKR/EphA2 (74%), patients with PKR/EphA2 (55%), and patients with PKR/EphA2 (55%) (p < 0.0001). We also found that the PKR:EphA2 (P/E) ratio was significantly associated with prognosis (p < 0.0001). Univariate and multivariate Cox analyses revealed that this P/E combination or ratio was an independent predictor of overall survival. In addition, induction of PKR expression reduced EphA2 protein expression levels in NSCLC cell lines.


CONCLUSIONS
PKR/EphA2 is a significant predictor of prognosis for NSCLC. PKR/EphA2 may be a promising approach to improving screening efficiency and predicting prognosis in patients with NSCLC.
Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Chengcheng
C
Guo
Ruping
R
Shao
Arlene M
AM
Correa
Carmen
C
Behrens
Faye M
FM
Johnson
Maria G
MG
Raso
Ludmila
L
Prudkin
Luisa M
LM
Solis
Maria I
MI
Nunez
Bingliang
B
Fang
Jack A
JA
Roth
Ignacio I
II
Wistuba
Stephen G
SG
Swisher
Tongyu
T
Lin
Apar
A
Pataer
D000230:Adenocarcinoma / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D008297:Male; D009367:Neoplasm Staging; D011379:Prognosis; D034741:RNA, Small Interfering / Q000235:genetics; D036104:Receptor, EphA2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015996:Survival Rate; D046888:Tissue Array Analysis; D014407:Tumor Cells, Cultured; D019892:eIF-2 Kinase / Q000378:metabolism*
D014408:Biomarkers, Tumor; D034741:RNA, Small Interfering; D036104:Receptor, EphA2; D019892:eIF-2 Kinase