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Prognostic significance of heat shock protein 90AA1 (HSP90α) in invasive breast cancer
  1. Sami A Alsaeed1,2,
  2. Michael Toss1,
  3. Mansour Alsaleem1,3,
  4. Mohammed Aleskandarany1,
  5. Chitra Joseph4,
  6. Sasagu Kurozumi1,5,
  7. Graham Ball6,
  8. Nigel Mongan7,8,
  9. Andrew Green1,
  10. Emad Rakha1,9
  1. 1Nottingham Breast Cancer Research Centre, Division of Cancer and Stem Cells, School of Medicine, Biodiscovery Institute, University of Nottingham, Nottingham, UK
  2. 2Faculty of Applied Medical Sciences, Northern Border University, Arar, Saudi Arabia
  3. 3Department of Applied Medical Sciences, Onizah Community College, Qassim University, Qassim, Saudi Arabia
  4. 4School of Medicine,The University of Nottingham and Nottingham University Hospitals NHS Trust, Nottingham City Hospital, Nottingham, UK
  5. 5Department of Breast Surgery, International University of Health and Welfare, Narita, Japan
  6. 6John van Geest Cancer Research Centre, School of Science and Technology, Nottingham Trent University, Nottingham, Notts, UK
  7. 7Faculty of Medicine and Health Sciences, Biodiscovery Institute, University of Nottingham, Nottingham, UK
  8. 8Department of Pharmacology, Weill Cornell Medicine, New York City, New York, USA
  9. 9Faculty of Medicine, Menoufyia University, Shebin al Kawm, Egypt
  1. Correspondence to Sami A Alsaeed, Nottingham Breast Cancer Research Centre, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham, Nottingham NG7 2RD, UK; sami.alsaeed{at}nottingham.ac.uk

Abstract

Aims The mechanisms that drive breast cancer (BC) progression and poor outcome are not fully understood. The human heat shock protein 90 alpha family class A member 1 (HSP90α) encoded by the HSP90ΑA1 gene has a vital role in cellular responses to stress and is implicated in the development and progression of many cancers. The current study aims to explore the clinical and prognostic importance of HSP90α in BC.

Methods The Molecular Taxonomy of Breast Cancer International Consortium (n=1980); The Cancer Genome Atlas (n=1097) and the Breast Cancer Gene-Expression Miner (Bc-GenExMiner) BC datasets (n=5056) were used to evaluate HSP90ΑA1 mRNA expression. HSP90α protein expression was further assessed using immunohistochemistry in a large (n=911) well-characterised BC series. The association between mRNA and protein expressions with other clinicopathological parameters and outcome was analysed.

Results High expression of HSP90ΑA1 both at the mRNA and protein levels was significantly associated with characteristics of BC poor prognosis, including high grade, lymphovascular invasion, poor Nottingham Prognostic Index and positive expression of p53 and PIK3CA. Outcome analysis revealed that high HSP90α protein expression is an independent predictor of shorter BC-specific survival.

Conclusion HSP90α can be used as a potential prognostic marker in BC. Further mechanistic studies are warranted to determine the underlying molecular mechanisms mediated by HSP90α in BC.

  • breast neoplasms
  • pathology
  • molecular
  • breast diseases
  • lymph nodes

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Footnotes

  • Handling editor Cheok Soon Lee.

  • Contributors SAA and ER conceived the project. SAA performed experiments and wrote the original draft manuscript. MT performed the pathological evaluation. MAls helped with analysis and interpretation of data. Paper writing was done by SAA, MT, MAle, MAls, CJ, SK, GB, NM, AG and ER. All authors reviewed the original draft manuscript and contributed to the editing and preparation of the final manuscript.

  • Funding Funding and support of the current study were made possible through the Saudi Arabia Ministry of Education, Northern Borders University (NBU).

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval The present study acquired the ethics approval of the North West—Greater Manchester Central Research Ethics Committee to use human tissue samples from the Nottingham Health Science Biobank (NHSB), along with the reference number 15/NW/0685. Before surgery, the informed consent was retrieved from all the study patients, informing them that their tissue materials will be used in research. The study followed the REMARK guidelines for tumour marker prognostic studies.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article or uploaded as supplemental information. Research involving human participants and/or animals: the researchers of the current study did not perform any experiment on either human or animal subjects. The researchers validate that the information used in the current study is available on request.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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