Whole Genome Transcriptome Analysis of the Association between Obesity and Triple-Negative Breast Cancer in Caucasian Women

Tarun K. K. Mamidi, Jiande Wu, Paul B. Tchounwou, Lucio Miele and Chindo Hicks
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Tarun K. K. Mamidi: Department of Genetics, Louisiana State University Health Sciences Center, School of Medicine, 533 Bolivar Street, New Orleans, LA 70112, USA
Jiande Wu: Department of Genetics, Louisiana State University Health Sciences Center, School of Medicine, 533 Bolivar Street, New Orleans, LA 70112, USA
Paul B. Tchounwou: NIH/NIMHD RCMI Center for Environmental Health, Jackson State University, 1400 Lynch Street, Box 18750, Jackson, MS 39217, USA
Lucio Miele: Department of Genetics, Louisiana State University Health Sciences Center, School of Medicine, 533 Bolivar Street, New Orleans, LA 70112, USA
Chindo Hicks: Department of Genetics, Louisiana State University Health Sciences Center, School of Medicine, 533 Bolivar Street, New Orleans, LA 70112, USA

IJERPH, 2018, vol. 15, issue 11, 1-16

Abstract: Background: Triple-negative breast cancer (TNBC) is the most aggressive form of breast cancer, with poor outcomes. The molecular basis of TNBC remains poorly understood. The objective of this exploratory study was to investigate the association between obesity and TNBC in premenopausal and postmenopausal Caucasian women using transcription profiling. Methods: We compared gene expression levels of tumor samples drawn from normal weight, overweight, and obese pre and postmenopausal women diagnosed with TNBC. We performed hierarchical clustering to assess similarity in patterns of gene expression profiles, and conducted network and pathway analysis to identify molecular networks and biological pathways. Results: We discovered gene signatures distinguishing normal weight from obese, normal weight from overweight, and overweight from obese individuals in both premenopausal and postmenopausal women. The analysis revealed molecular networks and biological pathways associating obesity with TNBC. The discovered pathways included the unfolded protein response, endoplasmic reticulum stress, B cell receptor, and autophagy signaling pathways in obese premenopausal women; and the integrin, axonal guidance, ERK/MAPK (extracellular-signal-regulated kinase/mitogen activated protein kinase) and glutathione biosynthesis signaling pathways in obese postmenopausal women. Conclusions: The results suggest that both overweight and obese status are associated with TNBC, highlighting the need for conformation of these results in independent studies.

Keywords: gene expression; obesity; triple-negative breast cancer (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2018
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