Department of Genetics, Louisiana State University Health Sciences Center, School of Medicine, 533 Bolivar Street, New Orleans, LA 70112, USA.
NIH/NIMHD RCMI Center for Environmental Health, Jackson State University, 1400 Lynch Street, Box 18750, Jackson, MS 39217, USA.
Int J Environ Res Public Health. 2018 Oct 23;15(11):2338. doi: 10.3390/ijerph15112338.
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.
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.
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.
The results suggest that both overweight and obese status are associated with TNBC, highlighting the need for conformation of these results in independent studies.
三阴性乳腺癌（TNBC）是最具侵袭性的乳腺癌，预后较差。TNBC 的分子基础仍知之甚少。本探索性研究的目的是使用转录谱分析来研究绝经前和绝经后白种女性肥胖与 TNBC 之间的关联。
我们比较了诊断为 TNBC 的正常体重、超重和肥胖绝经前和绝经后女性的肿瘤样本中的基因表达水平。我们进行了层次聚类以评估基因表达谱模式的相似性，并进行了网络和途径分析以确定分子网络和生物学途径。
我们发现了区分绝经前和绝经后正常体重与肥胖、正常体重与超重的基因特征。分析揭示了与肥胖相关的 TNBC 的分子网络和生物学途径。发现的途径包括绝经前肥胖女性的未折叠蛋白反应、内质网应激、B 细胞受体和自噬信号通路；以及绝经后肥胖女性的整合素、轴突导向、ERK/MAPK（细胞外信号调节激酶/丝裂原激活蛋白激酶）和谷胱甘肽生物合成信号通路。
结果表明，超重和肥胖状态均与 TNBC 相关，这突出表明需要在独立研究中证实这些结果。
