A novel role for Cathepsin S as a potential biomarker in triple negative breast cancer

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dc.contributor.author Wilkinson, Richard D. A.
dc.contributor.author Burden, Roberta E.
dc.contributor.author McDowell, Sara H.
dc.contributor.author McArt, Darragh G.
dc.contributor.author McQuaid, Stephen
dc.contributor.author Bingham, Victoria
dc.contributor.author Williams, Rich
dc.contributor.author Cox, Órla T.
dc.contributor.author O'Connor, Rosemary
dc.contributor.author McCabe, Nuala
dc.contributor.author Kennedy, Richard D.
dc.contributor.author Buckley, Niamh E.
dc.contributor.author Scott, Christopher J.
dc.date.accessioned 2019-11-01T08:10:44Z
dc.date.available 2019-11-01T08:10:44Z
dc.date.issued 2019-06-27
dc.identifier.citation Wilkinson, R.D., Burden, R.E., McDowell, S.H., McArt, D.G., McQuaid, S., Bingham, V., Williams, R., Cox, Ó.T., O’Connor, R., McCabe, N. and Kennedy, R.D., 2019. A Novel Role for Cathepsin S as a Potential Biomarker in Triple Negative Breast Cancer. Journal of Oncology, 2019. (3980273). DOI:10.1155/2019/3980273 en
dc.identifier.volume 2019 en
dc.identifier.startpage 1 en
dc.identifier.endpage 13 en
dc.identifier.issn 1687-8450
dc.identifier.uri http://hdl.handle.net/10468/8939
dc.identifier.doi 10.1155/2019/3980273 en
dc.description.abstract Cathepsin S (CTSS) has previously been implicated in a number of cancer types, where it is associated with poor clinical features and outcome. To date, patient outcome in breast cancer has not been examined with respect to this protease. Here, we carried out immunohistochemical (IHC) staining of CTSS using a breast cancer tissue microarray in patients who received adjuvant therapy. We scored CTSS expression in the epithelial and stromal compartments and evaluated the association of CTSS expression with matched clinical outcome data. We observed differences in outcome based on CTSS expression, with stromal-derived CTSS expression correlating with a poor outcome and epithelial CTSS expression associated with an improved outcome. Further subtype characterisation revealed high epithelial CTSS expression in TNBC patients with improved outcome, which remained consistent across two independent TMA cohorts. Further in silico gene expression analysis, using both in-house and publicly available datasets, confirmed these observations and suggested high CTSS expression may also be beneficial to outcome in ER-/HER2+ cancer. Furthermore, high CTSS expression was associated with the BL1 Lehmann subgroup, which is characterised by defects in DNA damage repair pathways and correlates with improved outcome. Finally, analysis of matching IHC analysis reveals an increased M1 (tumour destructive) polarisation in macrophage in patients exhibiting high epithelial CTSS expression. In conclusion, our observations suggest epithelial CTSS expression may be prognostic of improved outcome in TNBC. Improved outcome observed with HER2+ at the gene expression level furthermore suggests CTSS may be prognostic of improved outcome in ER- cancers as a whole. Lastly, from the context of these patients receiving adjuvant therapy and as a result of its association with BL1 subgroup CTSS may be elevated in patients with defects in DNA damage repair pathways, indicating it may be predictive of tumour sensitivity to DNA damaging agents. en
dc.description.sponsorship Medical Research Council (Confidence in Concept Funding); Breast Cancer Now (Scientific Fellowship NEB [2012MaySF122] and PhD Studentship [2017NovPhD1005]); Public Health Agency, Northern Ireland (Northern Ireland Biobank) en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher Hindawi en
dc.relation.uri https://www.hindawi.com/journals/jo/2019/3980273/
dc.rights © 2019 Richard D. A. Wilkinson et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. en
dc.rights.uri https://creativecommons.org/licenses/by/4.0/ en
dc.subject Cathepsin S (CTSS) en
dc.subject Breast cancer en
dc.subject Immunohistochemical (IHC) en
dc.title A novel role for Cathepsin S as a potential biomarker in triple negative breast cancer en
dc.type Article (peer-reviewed) en
dc.internal.authorcontactother Órla Cox, School of Biochemistry and Cell Biology, University College Cork, Cork, Ireland. +353-21-490-3000 Email: orla.cox@ucc.ie en
dc.internal.availability Full text available en
dc.description.version Published Version en
dc.contributor.funder Medical Research Council en
dc.contributor.funder Public Health Agency, Northern Ireland en
dc.contributor.funder Friends of the Cancer Centre en
dc.description.status Peer reviewed en
dc.identifier.journaltitle Journal of Oncology en
dc.internal.IRISemailaddress orla.cox@ucc.ie en
dc.identifier.articleid 3980273 en
dc.relation.project info:eu-repo/grantAgreement/RCUK/MRC/G0901615/GB/Molecular and pharmacological validation of Cathepsin S as a novel target in cancer treatment/ en
dc.identifier.eissn 1687-8469


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© 2019 Richard D. A. Wilkinson et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Except where otherwise noted, this item's license is described as © 2019 Richard D. A. Wilkinson et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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