Oncotarget

Research Papers:

Gene expression in “young adult type” breast cancer: a retrospective analysis

Rebecca H. Johnson _, Pingzhao Hu, Cheng Fan and Carey K. Anders

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Oncotarget. 2015; 6:13688-13702. https://doi.org/10.18632/oncotarget.4051

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Abstract

Rebecca H. Johnson1,*, Pingzhao Hu2,*, Cheng Fan3 and Carey K. Anders3,4

1 Seattle Children’s Hospital/University of Washington, Seattle, WA, USA

2 Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Canada

3 University of North Carolina, Lineberger Comprehensive Cancer Center, Chapel Hill, NC, USA

4 Department of Medicine, Division of Hematology-Oncology, University of North Carolina, Chapel Hill, NC, USA

* These authors are co-first authors

Correspondence to:

Rebecca Johnson, email:

Keywords: breast cancer, young, premenopausal, gene expression, survival

Received: January 01, 2015 Accepted: April 03, 2015 Published: May 09, 2015

Abstract

Background: Young women with breast cancer experience inferior outcome and commonly manifest aggressive biological subtypes. Data is controversial regarding biological differences between breast tumors in young (diagnosed at <40 years of age) versus older women. We hypothesize there may be age-related expression differences in key genes for proliferation, invasion and metastasis within and across breast cancer subtypes, and that these differences correlate with outcome.

Methods: Using clinically-annotated gene expression data from 778 breast tumors from three public databases, we compared clinico-pathologic characteristics, mRNA expression of 17 selected genes, and outcome, as a function of age (< 40 years vs. ≥ 40 years).

Results: 14 of 17 genes were differentially expressed in tumors of young vs. older women, 4 of which persisted after correction for subtype and grade (p ≤0.05). BUB1, KRT5, and MYCN were overexpressed and CXCL2 underexpressed in young women. In multivariate analysis, overexpression of cytokeratin genes predicted inferior DFS only for young women. Overexpression of ANGPTL4 strongly predicted inferior DFS in basal but not HER2-enriched tumors in young women. Overexpression of cytokeratin genes and MYBL2 and low SNAI1 expression correlated with inferior DFS in HER2-enriched tumors in younger women. Kaplan-Meier analysis within the basal and HER2-enriched subgroups showed that overexpression of cytokeratin genes was associated with inferior DFS for young, but not older women.

Conclusions: This preliminary study reveals age- and subtype-related differences in expression of key breast cancer genes for proliferation, invasion and metastasis, which correlate with prognostic differences in young women and suggest targeted therapies.


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