Obesity is a risk factor for the development of post-menopausal breast cancer. Breast white adipose tissue (WAT) inflammation, which is commonly found in women with excess body fat, is also associated with increased breast cancer risk. Both local and systemic effects are probably important for explaining the link between excess body fat, adipose inflammation and breast cancer. The first goal of this cross-sectional study of 196 women was to carry out transcriptome profiling to define the molecular changes that occur in the breast related to excess body fat and WAT inflammation. A second objective was to determine if commonly measured blood biomarkers of risk and prognosis reflect molecular changes in the breast. Breast WAT inflammation was assessed by immunohistochemistry. Bulk RNA-sequencing was carried out to assess gene expression in non-tumorous breast. Obesity and WAT inflammation were associated with a large number of differentially expressed genes and changes in multiple pathways linked to the development and progression of breast cancer. Altered pathways included inflammatory response, complement, KRAS signaling, tumor necrosis factor α signaling via NFkB, interleukin (IL)6-JAK-STAT3 signaling, epithelial mesenchymal transition, angiogenesis, interferon γ response and transforming growth factor (TGF)-β signaling. Increased expression of several drug targets such as aromatase, TGF-β1, IDO-1 and PD-1 were observed. Levels of various blood biomarkers including high sensitivity C-reactive protein, IL6, leptin, adiponectin, triglycerides, high-density lipoprotein cholesterol and insulin were altered and correlated with molecular changes in the breast. Collectively, this study helps to explain both the link between obesity and breast cancer and the utility of blood biomarkers for determining risk and prognosis.

中文翻译：

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血液生物标志物反映了肥胖和炎症对人类乳腺转录组的影响。


肥胖是绝经后乳腺癌发生的危险因素。乳房白色脂肪组织 (WAT) 炎症常见于体内脂肪过多的女性，也与乳腺癌风险增加有关。局部和全身效应对于解释体内过多脂肪、脂肪炎症和乳腺癌之间的联系可能很重要。这项针对 196 名女性的横断面研究的首要目标是进行转录组分析，以确定乳房中发生的与体内过多脂肪和 WAT 炎症相关的分子变化。第二个目标是确定通常测量的风险和预后血液生物标志物是否反映了乳房的分子变化。通过免疫组织化学评估乳房 WAT 炎症。进行大量 RNA 测序以评估非肿瘤乳腺中的基因表达。肥胖和 WAT 炎症与大量差异表达基因以及与乳腺癌发生和进展相关的多种途径的变化有关。改变的途径包括炎症反应、补体、KRAS 信号传导、通过 NFkB 的肿瘤坏死因子 α 信号传导、白细胞介素 (IL)6-JAK-STAT3 信号传导、上皮间质转化、血管生成、干扰素 γ 反应和转化生长因子 (TGF)-β 信号传导。观察到芳香酶、TGF-β1、IDO-1 和 PD-1 等多种药物靶标的表达增加。各种血液生物标志物（包括高敏C反应蛋白、IL6、瘦素、脂联素、甘油三酯、高密度脂蛋白胆固醇和胰岛素）的水平发生改变，并与乳房的分子变化相关。 总的来说，这项研究有助于解释肥胖与乳腺癌之间的联系以及血液生物标志物在确定风险和预后方面的效用。