relation: http://publicatio.bibl.u-szeged.hu/12588/
title: A Case-Matched Gender Comparison Transcriptomic Screen Identifies eIF4E and eIF5 as Potential Prognostic Markers in Male Breast Cancer.
creator:  Humphries Matthew P.
creator:  Sundara Rajan Sreekumar
creator:  Droop Alastair
creator:  Suleman C.A.
creator:  Carbone C.
creator:  Nilsson C.
creator:  Honarpisheh Hedieh
creator:  Cserni Gábor
creator:  Dent Jo
creator:  Fulford Laura
creator:  Jordan Lee B.
creator:  Jones J.  Louise
creator:  Kanthan Rani
creator:  Litwiniuk Maria
creator:  Kulka Janina
description: Purpose: Breast cancer affects both genders, but is understudied in men. Although still rare, male breast cancer (MBC) is being diagnosed more frequently. Treatments are wholly informed by clinical studies conducted in women, based on assumptions that underlying biology is similar.Experimental Design: A transcriptomic investigation of male and female breast cancer was performed, confirming transcriptomic data in silico Biomarkers were immunohistochemically assessed in 697 MBCs (n = 477, training; n = 220, validation set) and quantified  in pre- and posttreatment samples from an MBC patient receiving everolimus and PI3K/mTOR inhibitor.Results: Gender-specific gene expression patterns were identified. eIF transcripts were upregulated in MBC. eIF4E and eIF5 were negatively prognostic for overall survival alone (log-rank P = 0.013; HR = 1.77,  1.12-2.8 and P = 0.035; HR = 1.68, 1.03-2.74, respectively), or when coexpressed  (P = 0.01; HR = 2.66, 1.26-5.63), confirmed in the validation set. This remained  upon multivariate Cox regression analysis [eIF4E P = 0.016; HR = 2.38 (1.18-4.8), eIF5 P = 0.022; HR = 2.55 (1.14-5.7); coexpression P = 0.001; HR = 7.04 (2.22-22.26)]. Marked reduction in eIF4E and eIF5 expression was seen post BEZ235/everolimus, with extended survival.Conclusions: Translational initiation pathway inhibition could be of clinical utility in MBC patients overexpressing eIF4E and eIF5. With mTOR inhibitors that target this pathway now in the clinic,  these biomarkers may represent new targets for therapeutic intervention, although further independent validation is required. Clin Cancer Res; 1-9. (c)2016 AACR.
publisher: American Association for Cancer Research (AACR)
date: 2017
type: Folyóiratcikk
type: PeerReviewed
format: text
identifier: http://publicatio.bibl.u-szeged.hu/12588/1/2575.full.pdf
identifier:     Humphries Matthew P.;  Sundara Rajan Sreekumar;  Droop Alastair;  Suleman C.A.;  Carbone C.;  Nilsson C.;  Honarpisheh Hedieh;  Cserni Gábor;  Dent Jo;  Fulford Laura;  Jordan Lee B.;  Jones J. Louise;  Kanthan Rani;  Litwiniuk Maria;  Kulka Janina: A Case-Matched Gender Comparison Transcriptomic Screen Identifies eIF4E and eIF5 as Potential Prognostic Markers in Male Breast Cancer.   CCR CLINICAL CANCER RESEARCH, 23 (10).  pp. 2575-2583.  ISSN 1078-0432 (2017)     
identifier: doi:10.1158/1078-0432.CCR-16-1952
relation: 3203764
language: eng