DACH1: its role as a classifier of long term good prognosis in luminal breast cancer

Powe, DG, Dhondalay, GKR, Lemetre, C, Allen, T ORCID: https://orcid.org/0000-0001-6228-0237, Habashy, HO, Ellis, IO, Rees, R ORCID: https://orcid.org/0000-0002-4574-4746 and Ball, G ORCID: https://orcid.org/0000-0001-5828-7129, 2014. DACH1: its role as a classifier of long term good prognosis in luminal breast cancer. PLOS ONE, 9 (1). ISSN 1932-6203

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Abstract

Background: Oestrogen receptor (ER) positive (luminal) tumours account for the largest proportion of females with breast cancer. Theirs is a heterogeneous disease presenting clinical challenges in managing their treatment. Three main biological luminal groups have been identified but clinically these can be distilled into two prognostic groups in which Luminal A are accorded good prognosis and Luminal B correlate with poor prognosis. Further biomarkers are needed to attain classification consensus. Machine learning approaches like Artificial Neural Networks (ANNs) have been used for classification and identification of biomarkers in breast cancer using high throughput data. In this study, we have used an artificial neural network (ANN) approach to identify DACH1 as a candidate luminal marker and its role in predicting clinical outcome in breast cancer is assessed. Materials and methods: A reiterative ANN approach incorporating a network inferencing algorithm was used to identify ER- associated biomarkers in a publically available cDNA microarray dataset. DACH1 was identified in having a strong influence on ER associated markers and a positive association with ER. Its clinical relevance in predicting breast cancer specific survival was investigated by statistically assessing protein expression levels after immunohistochemistry in a series of unselected breast cancers, formatted as a tissue microarray. Results: Strong nuclear DACH1 staining is more prevalent in tubular and lobular breast cancer. Its expression correlated with ER-alpha positive tumours expressing PgR, epithelial cytokeratins (CK)18/19 and 'luminal-like' markers of good prognosis including FOXA1 and RERG (p , 0.05). DACH1 is increased in patients showing longer cancer specific survival and disease free interval and reduced metastasis formation (p , 0.001). Nuclear DACH1 showed a negative association with markers of aggressive growth and poor prognosis. Conclusion: Nuclear DACH1 expression appears to be a Luminal A biomarker predictive of good prognosis, but is not independent of clinical stage, tumour size, NPI status or systemic therapy.

Item Type:	Journal article
Publication Title:	PLOS ONE
Creators:	Powe, D.G., Dhondalay, G.K.R., Lemetre, C., Allen, T., Habashy, H.O., Ellis, I.O., Rees, R. and Ball, G.
Publisher:	Public Library of Science
Date:	2 January 2014
Volume:	9
Number:	1
ISSN:	1932-6203
Identifiers:	Number Type 10.1371/journal.pone.0084428 DOI
Rights:	Open access via the Creative Commons Attribution (CC BY) license
Divisions:	Schools > School of Science and Technology
Record created by:	EPrints Services
Date Added:	09 Oct 2015 09:43
Last Modified:	11 Oct 2021 11:15
URI:	https://irep.ntu.ac.uk/id/eprint/1777

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