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PMID: 24324792 Published · epublish English Journal Article Research Support, Non-U.S. Gov't

Differentially expressed transcripts and dysregulated signaling pathways and networks in African American breast cancer.

PloS one ·Vol. 8 ·No. 12 ·2013-00-00 ·Pages e82460

Stewart PA, Luks J, Roycik MD, Sang QX, Zhang J

Abstract

African Americans (AAs) have higher mortality rate from breast cancer than that of Caucasian Americans (CAs) even when socioeconomic factors are accounted for. To better understand the driving biological factors of this health disparity, we performed a comprehensive differential gene expression analysis, including subtype- and stage-specific analysis, using the breast cancer data in the Cancer Genome Atlas (TCGA). In total, 674 unique genes and other transcripts were found differentially expressed between these two populations. The numbers of differentially expressed genes between AA and CA patients increased in each stage of tumor progression: there were 26 in stage I, 161 in stage II, and 223 in stage III. Resistin, a gene that is linked to obesity, insulin resistance, and breast cancer, was expressed more than four times higher in AA tumors. An uncharacterized, long, non-coding RNA, LOC90784, was down-regulated in AA tumors, and its expression was inversely related to cancer stage and was the lowest in triple negative AA breast tumors. Network analysis showed increased expression of a majority of components in p53 and BRCA1 subnetworks in AA breast tumor samples, and members of the aurora B and polo-like kinase signaling pathways were also highly expressed. Higher gene expression diversity was observed in more advanced stage breast tumors suggesting increased genomic instability during tumor progression. Amplified resistin expression may indicate insulin-resistant type II diabetes and obesity are associated with AA breast cancer. Expression of LOC90784 may have a protective effect on breast cancer patients, and its loss, particularly in triple negative breast cancer, could be having detrimental effects. This work helps elucidate molecular mechanisms of breast cancer health disparity and identifies putative biomarkers and therapeutic targets such as resistin, and the aurora B and polo-like kinase signaling pathways for treating AA breast cancer patients.

MeSH Terms
Adult African Americans/genetics Aged Aged, 80 and over Breast Neoplasms/genetics,metabolism,pathology Female Gene Expression Profiling Gene Expression Regulation, Neoplastic Gene Regulatory Networks Humans Middle Aged RNA, Long Noncoding/genetics Signal Transduction Whites
Chemicals
RNA, Long Noncoding long non-coding RNA LOC90784, human
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Stewart Paul A
Department of Chemistry and Biochemistry, Florida State University, Tallahassee, Florida, United States of America.
Luks Jennifer
Roycik Mark D
Sang Qing-Xiang Amy
Zhang Jinfeng
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Article Info
Journal
PloS one
Abbr.
PLoS One
ISSN
1932-6203
DOI
10.1371/journal.pone.0082460
Published
2013-00-00
Epub
2013-00-04
Pages
e82460
Language
English
Region
United States
NLM ID
101285081
PMCID
PMC3853650
Subset
IM
External Links
PubMed source DOI: 10.1371/journal.pone.0082460 PMC Full Text View journal details
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