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Oncotarget. 2017 Mar 28;8(13):21733-21740. doi: 10.18632/oncotarget.15562.

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

Author information

1
Translational Research Unit, Albacete University Hospital and Centro Regional de Investigaciones Biomedicas (CRIB), Castilla La Mancha University, Albacete, Spain.
2
Yale Cancer Center, Yale University, New Haven, USA.
3
Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada.
4
Semmelweis University 2nd Department of Pediatrics, Budapest, Hungary.
5
MTA TTK Lendület Cancer Biomarker Research Group, Budapest, Hungary.
6
Cancer Research Center and CIBERONC, CSIC-University of Salamanca, Salamanca, Spain.

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.

KEYWORDS:

breast cancer; clinical outcome; luminal A; mitotic kinases

PMID:
28423514
PMCID:
PMC5400619
DOI:
10.18632/oncotarget.15562
[Indexed for MEDLINE]
Free PMC Article

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