1. Prognostic significance of combinations of RNA-dependent protein kinase and EphA2 biomarkers for NSCLC.
- Author
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Guo C, Shao R, Correa AM, Behrens C, Johnson FM, Raso MG, Prudkin L, Solis LM, Nunez MI, Fang B, Roth JA, Wistuba II, Swisher SG, Lin T, and Pataer A
- Subjects
- Adenocarcinoma metabolism, Adenocarcinoma pathology, Carcinoma, Non-Small-Cell Lung metabolism, Carcinoma, Non-Small-Cell Lung pathology, Carcinoma, Squamous Cell metabolism, Carcinoma, Squamous Cell pathology, Female, Follow-Up Studies, Humans, Immunoenzyme Techniques, Lung Neoplasms metabolism, Lung Neoplasms pathology, Male, Neoplasm Staging, Prognosis, RNA, Small Interfering genetics, Receptor, EphA2 antagonists & inhibitors, Receptor, EphA2 genetics, Survival Rate, Tissue Array Analysis, Tumor Cells, Cultured, Adenocarcinoma mortality, Biomarkers, Tumor metabolism, Carcinoma, Non-Small-Cell Lung mortality, Carcinoma, Squamous Cell mortality, Lung Neoplasms mortality, Receptor, EphA2 metabolism, eIF-2 Kinase metabolism
- Abstract
Introduction: 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.
- Published
- 2013
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