Decreased expression of ABAT and STC2 hallmarks ER-positive inflammatory breast cancer and endocrine therapy resistance in advanced disease.

Autor: Jansen MP; Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center Rotterdam, Wytemaweg 80, 3000 CA Rotterdam, The Netherlands. Electronic address: m.p.h.m.jansen@erasmusmc.nl., Sas L; Translational Cancer Research Unit, GZA Hospitals St-Augustinus, Oosterveldlaan 24, Antwerp B2610, Belgium; Department of Medical Oncology, University Hospital Antwerp, Wilrijkstraat 10, B2650 Antwerp, Belgium., Sieuwerts AM; Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center Rotterdam, Wytemaweg 80, 3000 CA Rotterdam, The Netherlands., Van Cauwenberghe C; Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium; Institute Born-Bunge, University of Antwerp, Antwerp, Belgium., Ramirez-Ardila D; Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center Rotterdam, Wytemaweg 80, 3000 CA Rotterdam, The Netherlands., Look M; Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center Rotterdam, Wytemaweg 80, 3000 CA Rotterdam, The Netherlands., Ruigrok-Ritstier K; Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center Rotterdam, Wytemaweg 80, 3000 CA Rotterdam, The Netherlands., Finetti P; Marseille Cancer Research Center (CRCM), UMR891 Inserm, Institut Paoli-Calmettes (IPC), Department of Molecular Oncology, Marseille, France., Bertucci F; Marseille Cancer Research Center (CRCM), UMR891 Inserm, Institut Paoli-Calmettes (IPC), Department of Molecular Oncology, Marseille, France., Timmermans MM; Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center Rotterdam, Wytemaweg 80, 3000 CA Rotterdam, The Netherlands., van Deurzen CH; Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center Rotterdam, Wytemaweg 80, 3000 CA Rotterdam, The Netherlands., Martens JW; Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center Rotterdam, Wytemaweg 80, 3000 CA Rotterdam, The Netherlands., Simon I; Research and Development, Agendia BV, Amsterdam, The Netherlands., Roepman P; Research and Development, Agendia BV, Amsterdam, The Netherlands., Linn SC; The Netherlands Cancer Institute, Amsterdam, The Netherlands., van Dam P; Translational Cancer Research Unit, GZA Hospitals St-Augustinus, Oosterveldlaan 24, Antwerp B2610, Belgium., Kok M; The Netherlands Cancer Institute, Amsterdam, The Netherlands., Lardon F; Department of Medical Oncology, University Hospital Antwerp, Wilrijkstraat 10, B2650 Antwerp, Belgium., Vermeulen PB; Translational Cancer Research Unit, GZA Hospitals St-Augustinus, Oosterveldlaan 24, Antwerp B2610, Belgium., Foekens JA; Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center Rotterdam, Wytemaweg 80, 3000 CA Rotterdam, The Netherlands., Dirix L; Translational Cancer Research Unit, GZA Hospitals St-Augustinus, Oosterveldlaan 24, Antwerp B2610, Belgium., Berns EM; Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center Rotterdam, Wytemaweg 80, 3000 CA Rotterdam, The Netherlands., Van Laere S; Translational Cancer Research Unit, GZA Hospitals St-Augustinus, Oosterveldlaan 24, Antwerp B2610, Belgium; Department of Oncology, KU Leuven, Leuven, Belgium.
Jazyk: angličtina
Zdroj: Molecular oncology [Mol Oncol] 2015 Jun; Vol. 9 (6), pp. 1218-33. Date of Electronic Publication: 2015 Mar 04.
DOI: 10.1016/j.molonc.2015.02.006
Abstrakt: Background: Patients with Estrogen Receptor α-positive (ER+) Inflammatory Breast Cancer (IBC) are less responsive to endocrine therapy compared with ER+ non-IBC (nIBC) patients. The study of ER+ IBC samples might reveal biomarkers for endocrine resistant breast cancer.
Materials & Methods: Gene expression profiles of ER+ samples from 201 patients were explored for genes that discriminated between IBC and nIBC. Classifier genes were applied onto clinically annotated expression data from 947 patients with ER+ breast cancer and validated with RT-qPCR for 231 patients treated with first-line tamoxifen. Relationships with metastasis-free survival (MFS) and progression-free survival (PFS) following adjuvant and first-line endocrine treatment, respectively, were investigated using Cox regression analysis.
Results: A metagene of six genes including the genes encoding for 4-aminobutyrate aminotransferase (ABAT) and Stanniocalcin-2 (STC2) were identified to distinguish 22 ER+ IBC from 43 ER+ nIBC patients and remained discriminatory in an independent series of 136 patients. The metagene and two genes were not prognostic in 517 (neo)adjuvant untreated lymph node-negative ER+ nIBC breast cancer patients. Only ABAT was related to outcome in 250 patients treated with adjuvant tamoxifen. Three independent series of in total 411 patients with advanced disease showed increased metagene scores and decreased expression of ABAT and STC2 to be correlated with poor first-line endocrine therapy outcome. The biomarkers remained predictive for first-line tamoxifen treatment outcome in multivariate analysis including traditional factors or published signatures. In an exploratory analysis, ABAT and STC2 protein expression levels had no relation with PFS after first-line tamoxifen.
Conclusions: This study utilized ER+ IBC to identify a metagene including ABAT and STC2 as predictive biomarkers for endocrine therapy resistance.
(Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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