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

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 postmenop...

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Autores principales: Mamidi, Tarun K. K., Wu, Jiande, Tchounwou, Paul B., Miele, Lucio, Hicks, Chindo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6265882/
https://www.ncbi.nlm.nih.gov/pubmed/30360534
http://dx.doi.org/10.3390/ijerph15112338
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author Mamidi, Tarun K. K.
Wu, Jiande
Tchounwou, Paul B.
Miele, Lucio
Hicks, Chindo
author_facet Mamidi, Tarun K. K.
Wu, Jiande
Tchounwou, Paul B.
Miele, Lucio
Hicks, Chindo
author_sort Mamidi, Tarun K. K.
collection PubMed
description 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.
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spelling pubmed-62658822018-12-15 Whole Genome Transcriptome Analysis of the Association between Obesity and Triple-Negative Breast Cancer in Caucasian Women Mamidi, Tarun K. K. Wu, Jiande Tchounwou, Paul B. Miele, Lucio Hicks, Chindo Int J Environ Res Public Health Article 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. MDPI 2018-10-23 2018-11 /pmc/articles/PMC6265882/ /pubmed/30360534 http://dx.doi.org/10.3390/ijerph15112338 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Mamidi, Tarun K. K.
Wu, Jiande
Tchounwou, Paul B.
Miele, Lucio
Hicks, Chindo
Whole Genome Transcriptome Analysis of the Association between Obesity and Triple-Negative Breast Cancer in Caucasian Women
title Whole Genome Transcriptome Analysis of the Association between Obesity and Triple-Negative Breast Cancer in Caucasian Women
title_full Whole Genome Transcriptome Analysis of the Association between Obesity and Triple-Negative Breast Cancer in Caucasian Women
title_fullStr Whole Genome Transcriptome Analysis of the Association between Obesity and Triple-Negative Breast Cancer in Caucasian Women
title_full_unstemmed Whole Genome Transcriptome Analysis of the Association between Obesity and Triple-Negative Breast Cancer in Caucasian Women
title_short Whole Genome Transcriptome Analysis of the Association between Obesity and Triple-Negative Breast Cancer in Caucasian Women
title_sort whole genome transcriptome analysis of the association between obesity and triple-negative breast cancer in caucasian women
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6265882/
https://www.ncbi.nlm.nih.gov/pubmed/30360534
http://dx.doi.org/10.3390/ijerph15112338
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