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Analysis of eIF4E and 4EBP1 mRNAs in head and neck cancer§

Authors

  • Gulshan Sunavala-Dossabhoy BDS, MDS, PhD,

    Corresponding author
    1. Department of Biochemistry and Molecular BiologyLouisiana State University Health Sciences Center and the Feist-Weiller Cancer Center, Shreveport, Louisiana, U.S.A
    • Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130
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  • Senthilnathan Palaniyandi PhD,

    1. Department of Biochemistry and Molecular BiologyLouisiana State University Health Sciences Center and the Feist-Weiller Cancer Center, Shreveport, Louisiana, U.S.A
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  • Cheryl Clark PhD,

    1. Department of Otolaryngology and Head and Neck Surgical OncologyLouisiana State University Health Sciences Center and the Feist-Weiller Cancer Center, Shreveport, Louisiana, U.S.A
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  • Cherie-Ann O. Nathan MD, FACS,

    1. Department of Otolaryngology and Head and Neck Surgical OncologyLouisiana State University Health Sciences Center and the Feist-Weiller Cancer Center, Shreveport, Louisiana, U.S.A
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  • Fleurette W. Abreo MD, FASCP,

    1. Department of PathologyLouisiana State University Health Sciences Center and the Feist-Weiller Cancer Center, Shreveport, Louisiana, U.S.A
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  • Gloria Caldito PhD

    1. Department of Bioinformatics and Computational Biology, Louisiana State University Health Sciences Center and the Feist-Weiller Cancer Center, Shreveport, Louisiana, U.S.A
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  • Supported by grant funds from the American Cancer Society and the Louisiana Gene Therapy Research Consortium.

  • The authors have no financial disclosures for this article.

  • §

    The authors have no conflicts of interest to disclose.

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.

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