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

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dc.contributor.authorWilkinson, Richard D. A.
dc.contributor.authorBurden, Roberta E.
dc.contributor.authorMcDowell, Sara H.
dc.contributor.authorMcArt, Darragh G.
dc.contributor.authorMcQuaid, Stephen
dc.contributor.authorBingham, Victoria
dc.contributor.authorWilliams, Rich
dc.contributor.authorCox, Órla T.
dc.contributor.authorO'Connor, Rosemary
dc.contributor.authorMcCabe, Nuala
dc.contributor.authorKennedy, Richard D.
dc.contributor.authorBuckley, Niamh E.
dc.contributor.authorScott, Christopher J.
dc.contributor.funderMedical Research Councilen
dc.contributor.funderPublic Health Agency, Northern Irelanden
dc.contributor.funderFriends of the Cancer Centreen
dc.date.accessioned2019-11-01T08:10:44Z
dc.date.available2019-11-01T08:10:44Z
dc.date.issued2019-06-27
dc.description.abstractCathepsin 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.sponsorshipMedical 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.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.articleid3980273en
dc.identifier.citationWilkinson, 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:10.1155/2019/3980273en
dc.identifier.doi10.1155/2019/3980273en
dc.identifier.eissn1687-8469
dc.identifier.endpage13en
dc.identifier.issn1687-8450
dc.identifier.journaltitleJournal of Oncologyen
dc.identifier.startpage1en
dc.identifier.urihttps://hdl.handle.net/10468/8939
dc.identifier.volume2019en
dc.language.isoenen
dc.publisherHindawien
dc.relation.projectinfo:eu-repo/grantAgreement/RCUK/MRC/G0901615/GB/Molecular and pharmacological validation of Cathepsin S as a novel target in cancer treatment/en
dc.relation.urihttps://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.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subjectCathepsin S (CTSS)en
dc.subjectBreast canceren
dc.subjectImmunohistochemical (IHC)en
dc.titleA novel role for Cathepsin S as a potential biomarker in triple negative breast canceren
dc.typeArticle (peer-reviewed)en
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