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A case-matched gend...
A case-matched gender comparison transcriptomic screen identifies eIF4E and eIF5 as potential prognostic markers in male breast cancer
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- Humphries, Matthew P. (author)
- University of Leeds,Univ Leeds, Leeds Inst Canc & Pathol, Leeds, W Yorkshire, England.
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- Rajan, Sreekumar Sundara (author)
- University of Leeds,Univ Leeds, Leeds Inst Canc & Pathol, Leeds, W Yorkshire, England.
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- Droop, Alastair (author)
- University of Leeds,Univ Leeds, Leeds Inst Canc & Pathol, Leeds, W Yorkshire, England.;Univ Leeds, MRC Med Bioinformat Ctr, Leeds, W Yorkshire, England.
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- Suleman, Charlotte A.B. (author)
- St James's University Hospital,St James Univ Hosp, Dept Histopathol, Leeds, W Yorkshire, England.
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- Carbone, Carmine (author)
- University Hospital Verona,Azienda Osped Univ Integrata, Ctr Comprehens Canc, Verona, Italy.
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- Nilsson, Cecilia (author)
- Uppsala universitet,Uppsala University,Västmanland Hospital,Centrum för klinisk forskning, Västerås,Institutionen för medicinska vetenskaper
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- Honarpisheh, Hedieh (author)
- University of Texas,Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.,Univ Leeds, Leeds Inst Canc & Pathol, Leeds, W Yorkshire, England.
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- Cserni, Gabor (author)
- Bács-Kiskun County Teaching Hospital,Bacs Kiskun Cty Teaching Hosp, Dept Pathol, Kecskemet, Hungary.
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- Dent, Jo (author)
- Calderdale Hospital,Calderdale Hosp, Halifax, England.
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- Fulford, Laura (author)
- Surrey and Sussex Healthcare NHS Trust,Surrey & Sussex NHS Trust, Redhill, Surrey, England.
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- Jordan, Lee B. (author)
- Ninewells Hospital and Medical School,Univ Dundee, NHS Tayside, Dundee, Scotland.
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- Jones, J. Louise (author)
- Institute of Cancer Research London,Barts Canc Inst, London, England.
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- Kanthan, Rani (author)
- Univ Saskatchewan, Dept Pathol & Lab Med, Saskatoon, SK, Canada.
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- Litwiniuk, Maria (author)
- Poznan University of Medical Sciences,Poznan Univ Med Sci, Greater Poland Canc Ctr, Poznan, Poland.
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- Di Benedetto, Anna (author)
- Regina Elena Inst Canc Res, Dept Pathol, Rome, Italy.
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- Mottolese, Marcella (author)
- National Cancer Institute Regina Elena,Regina Elena Inst Canc Res, Dept Pathol, Rome, Italy.,Queen Elizabeth Hosp Birmingham, Dept Cellular Pathol, Birmingham, W Midlands, England.;Univ Birmingham, Birmingham, W Midlands, England.
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- Provenzano, Elena (author)
- Addenbrooke's Hospital,Addenbrookes Hosp, Dept Histopathol, Cambridge, England.
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- Shousha, Sami (author)
- Charing Cross Hospital,Imperial Coll Healthcare NHS Trust, Dept Histopathol, London, England.;Charing Cross Hosp, Imperial Coll, London, England.
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- Stephens, Mark (author)
- University Hospital of North Staffordshire,Univ Hosp North Staffordshire, Stoke On Trent, Staffs, England.
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- Walker, Rosemary A. (author)
- University of Leicester,Univ Leicester, Canc Studies & Mol Med, Leicester, Leics, England.
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- Kulka, Janina (author)
- Semmelweis University,Semmelweis Univ, Dept Pathol 2, Budapest, Hungary.
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- Ellis, Ian O. (author)
- Nottingham City Hospital,Nottingham City Hosp, Fac Med & Hlth Sci, Nottingham, England.
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- Jeffery, Margaret (author)
- Queen Alexandra Hospital,Queen Alexandra Hosp, Pathol Ctr, Dept Histopathol, Portsmouth, Hants, England.
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- Thygesen, Helene H. (author)
- University of Leeds
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- Cappelletti, Vera (author)
- Istituto Nazionale dei Tumori,Fdn IRCCS Ist Nazl Tumori, Dept Expt Oncol & Mol Med, Milan, Italy.
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- Daidone, Maria G. (author)
- Istituto Nazionale dei Tumori,Fdn IRCCS Ist Nazl Tumori, Dept Expt Oncol & Mol Med, Milan, Italy.
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- Hedenfalk, Ingrid A. (author)
- Lund University,Lunds universitet,Create Health,Annan verksamhet, LTH,Lunds Tekniska Högskola,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Bröst- och ovarialcancer,Forskargrupper vid Lunds universitet,Other operations, LTH,Faculty of Engineering, LTH,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Breast and Ovarian Cancer Genomics,Lund University Research Groups,Lund Univ, Dept Oncol & Pathol, Clin Sci, Lund, Sweden.;Lund Univ, CREATE Hlth Strateg Ctr Translat Canc Res, Lund, Sweden.
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- Fjällskog, Marie-Louise (author)
- Uppsala universitet,Uppsala University,Onkologisk endokrinologi
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- Melisi, Davide (author)
- University of Verona,University Hospital Verona,Azienda Osped Univ Integrata, Ctr Comprehens Canc, Verona, Italy.;Univ Verona, Dept Med, Digest Mol Clin Oncol Res Unit, Verona, Italy.
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- Stead, Lucy F. (author)
- University of Leeds,Univ Leeds, Leeds Inst Canc & Pathol, Leeds, W Yorkshire, England.
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- Shaaban, Abeer M. (author)
- University of Birmingham
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- Speirs, Valerie (author)
- University of Leeds,Univ Leeds, Leeds Inst Canc & Pathol, Leeds, W Yorkshire, England.
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University of Leeds Univ Leeds, Leeds Inst Canc & Pathol, Leeds, W Yorkshire, England (creator_code:org_t)
- 2017
- 2017
- English 9 s.
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In: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 23:10, s. 2575-2583
- Related links:
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http://dx.doi.org/10...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Humphries, Matth ...
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Rajan, Sreekumar ...
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Droop, Alastair
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Suleman, Charlot ...
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Carbone, Carmine
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Nilsson, Cecilia
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Honarpisheh, Hed ...
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Cserni, Gabor
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Dent, Jo
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Fulford, Laura
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Jordan, Lee B.
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Jones, J. Louise
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Kanthan, Rani
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Litwiniuk, Maria
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Di Benedetto, An ...
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Mottolese, Marce ...
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Provenzano, Elen ...
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Shousha, Sami
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Stephens, Mark
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Walker, Rosemary ...
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Kulka, Janina
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Ellis, Ian O.
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Jeffery, Margare ...
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Thygesen, Helene ...
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Cappelletti, Ver ...
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Daidone, Maria G ...
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Hedenfalk, Ingri ...
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Fjällskog, Marie ...
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Melisi, Davide
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Stead, Lucy F.
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Shaaban, Abeer M ...
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Speirs, Valerie
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
- Articles in the publication
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Clinical Cancer ...
- By the university
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Lund University
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Uppsala University