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.; Johnson, C.; Moseley, P.M.; Ball, G.R.; Pockley, A.G.; Ellis, I.O.; Rees, R.C.; Chan, S.Y.T.

Abstract

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 ¼ 2147): early primary (EP-BC; n ¼ 1676); primary oestrogen receptor-negative (PER-BC; n ¼ 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 ¼ 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 (HAGE þ ) and was associated with aggressive
clinico-pathological features (Pso0.01). Furthermore, HAGE þ expression was associated with poor prognosis in both univariate and multivariate analysis (Pso0.001). Patients with HAGE þ did not benefit from hormonal therapy in high-risk ER-positive disease. HAGE þ and TILs were found to be independent predictors for pathological complete response to neoadjuvant-ACT; Po0.001. A statistically significant loss of HAGE expression following neoadjuvant-ACT was found (P ¼ 0.000001), and progression-free survival was worse in those patients who had HAGE þ residual disease (P ¼ 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.

• Journal Article Type: Article
• Acceptance Date: Mar 5, 2014
• Online Publication Date: Apr 22, 2014
• Publication Date: 2014-05
• Deposit Date: Dec 5, 2018
• Publicly Available Date: Apr 9, 2019
• Journal: British Journal of Cancer
• Print ISSN: 0007-0920
• Electronic ISSN: 1532-1827
• Publisher: Cancer Research UK
• Peer Reviewed: Peer Reviewed
• Volume: 110
• Issue: 10
• Pages: 2450-2461
• DOI: https://doi.org/10.1038/bjc.2014.168
• Public URL: https://nottingham-repository.worktribe.com/output/1371112
• Publisher URL: https://www.nature.com/articles/bjc2014168