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
- breast diseases
- lymph nodes
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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.
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