1. Analysis of eIF4E and 4EBP1 mRNAs in head and neck cancer.
- Author
-
Sunavala-Dossabhoy G, Palaniyandi S, Clark C, Nathan CO, Abreo FW, and Caldito G
- Subjects
- Adaptor Proteins, Signal Transducing genetics, Adaptor Proteins, Signal Transducing metabolism, Adult, Aged, Biopsy, Needle, Carcinoma genetics, Carcinoma mortality, Carcinoma, Squamous Cell, Chi-Square Distribution, Cohort Studies, Disease Progression, Eukaryotic Initiation Factor-4E genetics, Female, Head and Neck Neoplasms genetics, Head and Neck Neoplasms mortality, Humans, Male, Middle Aged, Neoplasm Invasiveness pathology, Neoplasm Recurrence, Local genetics, Neoplasm Staging, Neoplasms, Squamous Cell genetics, Neoplasms, Squamous Cell mortality, Predictive Value of Tests, Prognosis, RNA-Binding Proteins genetics, RNA-Binding Proteins metabolism, Reverse Transcriptase Polymerase Chain Reaction, Risk Assessment, Sensitivity and Specificity, Squamous Cell Carcinoma of Head and Neck, Statistics, Nonparametric, Survival Analysis, Tissue Culture Techniques, Biomarkers, Tumor metabolism, Carcinoma pathology, Eukaryotic Initiation Factor-4E metabolism, Head and Neck Neoplasms pathology, Neoplasm Recurrence, Local metabolism, Neoplasms, Squamous Cell pathology, RNA, Messenger analysis
- Abstract
Objectives/hypothesis: The eukaryotic translation initiation factor 4E (eIF4E) in conjunction with its binding protein, 4EBP1, regulates the translation of cap-dependent mRNAs. An aberrant increase in eIF4E shifts the balance in favor of translation of transcripts that promote cell proliferation and malignancy. eIF4E protein is commonly elevated in head and neck squamous cell carcinomas (HNSCC), and its overexpression is associated with increased recurrence. An underlying mechanism for eIF4E overexpression is gene amplification, and we wanted to determine whether eIF4E mRNA could serve as a prognostic maker of HNSCC., Methods: Tumor specimens from 26 HNSCC patients and oral tissues from 17 control subjects were examined for eIF4E and 4EBP1 by semiquantitative RT-PCR and correlated with clinical and pathologic findings., Results: Unlike eIF4E mRNA alone, expression of eIF4E relative to 4EBP1 was a more precise predictor of HNSCC and its progression (P < .01, Wilcoxon rank sum test). Eight of 26 patients (31%) had elevated eIF4E:4EBP1 (4E:4EBP1; >25), and 7 of these (87.5%) had recurrence. Alternately, from 18 patients with low 4E:4EBP1 (<25; 69%), only 5 patients had recurrence (30.1%). To determine the probability of no recurrence, Kaplan-Meier analysis showed significantly poor disease-free survival in patients with elevated 4E:4EBP1 than those with low ratios (P < .01, log rank test)., Conclusions: Elevated 4E:4EBP1 significantly correlated with increased disease recurrence. Because 4EBP1 modulates eIF4E activity, our results highlight the importance of incorporating a joint analysis of eIF4E and 4EBP1 mRNAs in HNSCC patient care decisions., (Copyright © 2011 The American Laryngological, Rhinological, and Otological Society, Inc.)
- Published
- 2011
- Full Text
- View/download PDF