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01-02-2019 | Preclinical study

Combinatorial expression of microtubule-associated EB1 and ATIP3 biomarkers improves breast cancer prognosis

Authors: Sylvie Rodrigues-Ferreira, Anne Nehlig, Clarisse Monchecourt, Sarah Nasr, Laetitia Fuhrmann, Magali Lacroix-Triki, Ingrid Garberis, Véronique Scott, Suzette Delaloge, Barbara Pistilli, Philippe Vielh, Thierry Dubois, Anne Vincent-Salomon, Fabrice André, Clara Nahmias

Published in: Breast Cancer Research and Treatment | Issue 3/2019

Abstract

Purpose

The identification of molecular biomarkers for classification of breast cancer is needed to better stratify the patients and guide therapeutic decisions. The aim of this study was to investigate the value of MAPRE1 gene encoding microtubule-end binding proteins EB1 as a biomarker in breast cancer and evaluate whether combinatorial expression of MAPRE1 and MTUS1 gene encoding EB1-negative regulator ATIP3 may improve breast cancer diagnosis and prognosis.

Methods

Probeset intensities for MAPRE1 and MTUS1 genes were retrieved from Exonhit splice array analyses of 45 benign and 120 malignant breast tumors for diagnostic purposes. Transcriptomic analyses (U133 Affymetrix array) of one exploratory cohort of 150 invasive breast cancer patients and two independent series of 130 and 155 samples were compared with clinical data of the patients for prognostic studies. A tissue microarray from an independent cohort of 212 invasive breast tumors was immunostained with anti-EB1 and anti-ATIP3 antibodies.

Results

We show that MAPRE1 gene is a diagnostic and prognostic biomarker in breast cancer. High MAPRE1 levels correlate with tumor malignancy, high histological grade and poor clinical outcome. Combination of high-MAPRE1 and low-MTUS1 levels in tumors is significantly associated with tumor aggressiveness and reduced patient survival. IHC studies of combined EB1/ATIP3 protein expression confirmed these results.

Conclusions

These studies emphasize the importance of studying combinatorial expression of EB1 and ATIP3 genes and proteins rather than each biomarker alone. A population of highly aggressive breast tumors expressing high-EB1/low-ATIP3 may be considered for the development of new molecular therapies.

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Title: Combinatorial expression of microtubule-associated EB1 and ATIP3 biomarkers improves breast cancer prognosis
Authors: Sylvie Rodrigues-Ferreira
Anne Nehlig
Clarisse Monchecourt
Sarah Nasr
Laetitia Fuhrmann
Magali Lacroix-Triki
Ingrid Garberis
Véronique Scott
Suzette Delaloge
Barbara Pistilli
Philippe Vielh
Thierry Dubois
Anne Vincent-Salomon
Fabrice André
Clara Nahmias
Publication date: 01-02-2019
Publisher: Springer US
Published in: Breast Cancer Research and Treatment / Issue 3/2019
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-018-5026-1

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