HAGE (DDX43) is a biomarker for poor prognosis and a predictor of chemotherapy response in breast cancer

Abdel-Fatah, T.M.A., McArdle, S.E.B. ORCID: 0000-0001-6929-9782, Johnson, C., Moseley, P.M., Ball, G.R. ORCID: 0000-0001-5828-7129, Pockley, A.G. ORCID: 0000-0001-9593-6431, Ellis, I.O., Rees, R.C. ORCID: 0000-0002-4574-4746 and Chan, S.Y.T., 2014. HAGE (DDX43) is a biomarker for poor prognosis and a predictor of chemotherapy response in breast cancer. British Journal of Cancer, 110 (10), pp. 2450-2461. ISSN 1532-1827

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Background: HAGE protein is a known immunogenic cancer-specific antigen. Methods: The biological, prognostic and predictive values of HAGE expression was studied using immunohistochemistry in three cohorts of patients with BC (n=2147): early primary (EP-BC; n=1676); primary oestrogen receptor-negative (PER-BC; n=275) treated with adjuvant anthracycline-combination therapies (Adjuvant-ACT); and primary locally advanced disease (PLA-BC) who received neo-adjuvant anthracycline-combination therapies (Neo-adjuvant-ACT; n=196). The relationship between HAGE expression and the tumour-infiltrating lymphocytes (TILs) in matched prechemotherapy and postchemotherapy samples were investigated. Results: Eight percent of patients with EP-BC exhibited high HAGE expression (HAGEþ) and was associated with aggressive clinico-pathological features (Ps<0.01). Furthermore, HAGEþexpression was associated with poor prognosis in both univariate and multivariate analysis (Ps<0.001). Patients with HAGE+ did not benefit from hormonal therapy in high-risk ER-positive disease. HAGE+ and TILs were found to be independent predictors for pathological complete response to neoadjuvant-ACT; P<0.001. A statistically significant loss of HAGE expression following neoadjuvant-ACT was found (P=0.000001), and progression-free survival was worse in those patients who had HAGE+ residual disease (P=0.0003). Conclusions: This is the first report to show HAGE to be a potential prognostic marker and a predictor of response to ACT in patients with BC.

Item Type: Journal article
Publication Title: British Journal of Cancer
Creators: Abdel-Fatah, T.M.A., McArdle, S.E.B., Johnson, C., Moseley, P.M., Ball, G.R., Pockley, A.G., Ellis, I.O., Rees, R.C. and Chan, S.Y.T.
Publisher: Nature Publishing Group
Date: 2014
Volume: 110
Number: 10
ISSN: 1532-1827
Divisions: Schools > School of Science and Technology
Record created by: EPrints Services
Date Added: 09 Oct 2015 10:09
Last Modified: 11 Oct 2021 13:26
URI: https://irep.ntu.ac.uk/id/eprint/8668

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