Combined analysis of eIF4E and 4E-binding protein expression predicts breast cancer survival and estimates eIF4E activity

L J Coleman, M B Peter, T J Teall, R A Brannan, A M Hanby, H Honarpisheh, A M Shaaban, L Smith, V Speirs, E T Verghese, J N McElwaine, T A Hughes

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Abstract

Increased eukaryotic translation initiation factor 4E (eIF4E) expression occurs in many cancers, and makes fundamental contributions to carcinogenesis by stimulating the expression of cancer-related genes at post-transcriptional levels. This key role is highlighted by the facts that eIF4E levels can predict prognosis, and that eIF4E is an established therapeutic target. However, eIF4E activity is a complex function of expression levels and phosphorylation statuses of eIF4E and eIF4E-binding proteins (4E-BPs). Our hypothesis was that the combined analyses of these pathway components would allow insights into eIF4E activity and its influence on cancer. We have determined expression levels of eIF4E, 4E-BP1, 4E-BP2 and phosphorylated 4E-BP1 within 424 breast tumours, and have carried out analyses to combine these and relate the product to patient survival, in order to estimate eIF4E activity. We show that this analysis gives greater prognostic insights than that of eIF4E alone. We show that eIF4E and 4E-BP expression are positively associated, and that 4E-BP2 has a stronger influence on cancer behaviour than 4E-BP1. Finally, we examine eIF4E, estimated eIF4E activity, and phosphorylated 4E-BP1 as potential predictive biomarkers for eIF4E-targeted therapies, and show that each determines selection of different patient groups. We conclude that eIF4E's influence on cancer survival is modulated substantially by 4E-BPs, and that combined pathway analyses can estimate functional eIF4E.

Original languageEnglish
Pages (from-to)1393-1399
Number of pages7
JournalBritish Journal of Cancer
Volume100
Issue number9
DOIs
Publication statusPublished - 5 May 2009

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Eukaryotic Initiation Factor-4E
Eukaryotic Initiation Factors
Carrier Proteins
Breast Neoplasms
Survival
Neoplasms
Neoplasm Genes

Keywords

  • Adaptor Proteins, Signal Transducing
  • Breast Neoplasms
  • Cohort Studies
  • Eukaryotic Initiation Factor-4E
  • Eukaryotic Initiation Factors
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Phosphoproteins
  • Phosphorylation
  • Prognosis
  • Retrospective Studies
  • Survival Analysis
  • Journal Article
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

Cite this

Coleman, L. J., Peter, M. B., Teall, T. J., Brannan, R. A., Hanby, A. M., Honarpisheh, H., ... Hughes, T. A. (2009). Combined analysis of eIF4E and 4E-binding protein expression predicts breast cancer survival and estimates eIF4E activity. British Journal of Cancer, 100(9), 1393-1399. https://doi.org/10.1038/sj.bjc.6605044

Combined analysis of eIF4E and 4E-binding protein expression predicts breast cancer survival and estimates eIF4E activity. / Coleman, L J; Peter, M B; Teall, T J; Brannan, R A; Hanby, A M; Honarpisheh, H; Shaaban, A M; Smith, L; Speirs, V; Verghese, E T; McElwaine, J N; Hughes, T A.

In: British Journal of Cancer, Vol. 100, No. 9, 05.05.2009, p. 1393-1399.

Research output: Contribution to journalArticle

Coleman, LJ, Peter, MB, Teall, TJ, Brannan, RA, Hanby, AM, Honarpisheh, H, Shaaban, AM, Smith, L, Speirs, V, Verghese, ET, McElwaine, JN & Hughes, TA 2009, 'Combined analysis of eIF4E and 4E-binding protein expression predicts breast cancer survival and estimates eIF4E activity', British Journal of Cancer, vol. 100, no. 9, pp. 1393-1399. https://doi.org/10.1038/sj.bjc.6605044
Coleman, L J ; Peter, M B ; Teall, T J ; Brannan, R A ; Hanby, A M ; Honarpisheh, H ; Shaaban, A M ; Smith, L ; Speirs, V ; Verghese, E T ; McElwaine, J N ; Hughes, T A. / Combined analysis of eIF4E and 4E-binding protein expression predicts breast cancer survival and estimates eIF4E activity. In: British Journal of Cancer. 2009 ; Vol. 100, No. 9. pp. 1393-1399.
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AU - Coleman, L J

AU - Peter, M B

AU - Teall, T J

AU - Brannan, R A

AU - Hanby, A M

AU - Honarpisheh, H

AU - Shaaban, A M

AU - Smith, L

AU - Speirs, V

AU - Verghese, E T

AU - McElwaine, J N

AU - Hughes, T A

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N2 - Increased eukaryotic translation initiation factor 4E (eIF4E) expression occurs in many cancers, and makes fundamental contributions to carcinogenesis by stimulating the expression of cancer-related genes at post-transcriptional levels. This key role is highlighted by the facts that eIF4E levels can predict prognosis, and that eIF4E is an established therapeutic target. However, eIF4E activity is a complex function of expression levels and phosphorylation statuses of eIF4E and eIF4E-binding proteins (4E-BPs). Our hypothesis was that the combined analyses of these pathway components would allow insights into eIF4E activity and its influence on cancer. We have determined expression levels of eIF4E, 4E-BP1, 4E-BP2 and phosphorylated 4E-BP1 within 424 breast tumours, and have carried out analyses to combine these and relate the product to patient survival, in order to estimate eIF4E activity. We show that this analysis gives greater prognostic insights than that of eIF4E alone. We show that eIF4E and 4E-BP expression are positively associated, and that 4E-BP2 has a stronger influence on cancer behaviour than 4E-BP1. Finally, we examine eIF4E, estimated eIF4E activity, and phosphorylated 4E-BP1 as potential predictive biomarkers for eIF4E-targeted therapies, and show that each determines selection of different patient groups. We conclude that eIF4E's influence on cancer survival is modulated substantially by 4E-BPs, and that combined pathway analyses can estimate functional eIF4E.

AB - Increased eukaryotic translation initiation factor 4E (eIF4E) expression occurs in many cancers, and makes fundamental contributions to carcinogenesis by stimulating the expression of cancer-related genes at post-transcriptional levels. This key role is highlighted by the facts that eIF4E levels can predict prognosis, and that eIF4E is an established therapeutic target. However, eIF4E activity is a complex function of expression levels and phosphorylation statuses of eIF4E and eIF4E-binding proteins (4E-BPs). Our hypothesis was that the combined analyses of these pathway components would allow insights into eIF4E activity and its influence on cancer. We have determined expression levels of eIF4E, 4E-BP1, 4E-BP2 and phosphorylated 4E-BP1 within 424 breast tumours, and have carried out analyses to combine these and relate the product to patient survival, in order to estimate eIF4E activity. We show that this analysis gives greater prognostic insights than that of eIF4E alone. We show that eIF4E and 4E-BP expression are positively associated, and that 4E-BP2 has a stronger influence on cancer behaviour than 4E-BP1. Finally, we examine eIF4E, estimated eIF4E activity, and phosphorylated 4E-BP1 as potential predictive biomarkers for eIF4E-targeted therapies, and show that each determines selection of different patient groups. We conclude that eIF4E's influence on cancer survival is modulated substantially by 4E-BPs, and that combined pathway analyses can estimate functional eIF4E.

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KW - Eukaryotic Initiation Factors

KW - Female

KW - Gene Expression Regulation, Neoplastic

KW - Humans

KW - Immunohistochemistry

KW - Phosphoproteins

KW - Phosphorylation

KW - Prognosis

KW - Retrospective Studies

KW - Survival Analysis

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

KW - Research Support, U.S. Gov't, Non-P.H.S.

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DO - 10.1038/sj.bjc.6605044

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VL - 100

SP - 1393

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JO - British Journal of Cancer

JF - British Journal of Cancer

SN - 0007-0920

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