Mitotic read-out genes confer poor outcome in luminal A breast cancer tumors

Javier Pérez-Peña; Ana Alcaraz-Sanabria; Cristina Nieto-Jiménez; Raquel Páez; Verónica Corrales-Sánchez; Leticia Serrano-Oviedo; Vikram B. Wali; Gauri A. Patwardhan; Eitan Amir; Balázs Győrffy; Atanasio Pandiella; Alberto Ocaña

doi:10.18632/oncotarget.15562

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Research Papers:

Mitotic read-out genes confer poor outcome in luminal A breast cancer tumors

Javier Pérez-Peña, Ana Alcaraz-Sanabria, Cristina Nieto-Jiménez, Raquel Páez, Verónica Corrales-Sánchez, Leticia Serrano-Oviedo, Vikram B. Wali, Gauri A. Patwardhan, Eitan Amir, Balázs Győrffy, Atanasio Pandiella and Alberto Ocaña _

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Oncotarget. 2017; 8:21733-21740. https://doi.org/10.18632/oncotarget.15562

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Abstract

Javier Pérez-Peña1,*, Ana Alcaraz-Sanabria1,*, Cristina Nieto-Jiménez1,*, Raquel Páez1, Verónica Corrales-Sánchez1, Leticia Serrano-Oviedo1, Vikram B. Wali2, Gauri A. Patwardhan2, Eitan Amir3, Balázs Győrffy4,5, Atanasio Pandiella6, Alberto Ocaña1

1Translational Research Unit, Albacete University Hospital and Centro Regional de Investigaciones Biomedicas (CRIB), Castilla La Mancha University, Albacete, Spain

2Yale Cancer Center, Yale University, New Haven, USA

3Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada

4Semmelweis University, 2nd Department of Pediatrics, Budapest, Hungary

5MTA TTK Lendület Cancer Biomarker Research Group, Budapest, Hungary

6Cancer Research Center and CIBERONC, CSIC-University of Salamanca, Salamanca, Spain

*These authors have contributed equally to this work

Correspondence to:

Alberto Ocaña, email: [email protected]

Keywords: breast cancer, luminal A, mitotic kinases, clinical outcome

Received: October 19, 2016 Accepted: January 16, 2017 Published: February 21, 2017

ABSTRACT

Luminal breast tumors have been classified into A and B subgroups, with the luminal A being associated with a more favorable clinical outcome. Unfortunately, luminal A tumors do not have a universally good prognosis. We used transcriptomic analyses using public datasets to evaluate the differential expression between normal breast tissue and breast cancer, focusing on upregulated genes included in cell cycle function. Association of selected genes with relapse free survival (RFS) and overall survival (OS) was performed using the KM Plotter Online Tool (http://www.kmplot.com). Seventy-seven genes were differentially expressed between normal and malignant breast tissue. Only five genes were associated with poor RFS and OS. The mitosis-related genes GTSE1, CDCA3, FAM83D and SMC4 were associated with poor outcome specifically in Luminal A tumors. The combination of FAM83D and CDCA3 for RFS and GTSE1 alone for OS showed the better prediction for clinical outcome. CDCA3 was amplified in 3.4% of the tumors, and FAM83D and SMC4 in 2.3% and 2.2%, respectively. In conclusion, we describe a set of genes that predict detrimental outcome in Luminal A tumors. These genes may have utility for stratification in trials of antimitotic agents or cytotoxic chemotherapy, or as candidates for direct target inhibition.

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Research Papers:

Mitotic read-out genes confer poor outcome in luminal A breast cancer tumors

Abstract