Hormone and receptor activator of NF-κB (RANK) pathway gene expression in plasma and mammographic breast density in postmenopausal women.

IF 6.2 1区医学 Q1 ONCOLOGY

Breast Cancer Research Pub Date : 2022-04-14 DOI:10.1186/s13058-022-01522-2

Rachel Mintz, Mei Wang, Shuai Xu, Graham A Colditz, Chris Markovic, Adetunji T Toriola

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引用次数: 0

Abstract

Background: Hormones impact breast tissue proliferation. Studies investigating the associations of circulating hormone levels with mammographic breast density have reported conflicting results. Due to the limited number of studies, we investigated the associations of hormone gene expression as well as their downstream mediators within the plasma with mammographic breast density in postmenopausal women.

Methods: We recruited postmenopausal women at their annual screening mammogram at Washington University School of Medicine, St. Louis. We used the NanoString nCounter platform to quantify gene expression of hormones (prolactin, progesterone receptor (PGR), estrogen receptor 1 (ESR1), signal transducer and activator of transcription (STAT1 and STAT5), and receptor activator of nuclear factor-kB (RANK) pathway markers (RANK, RANKL, osteoprotegerin, TNFRSF18, and TNFRSF13B) in plasma. We used Volpara to measure volumetric percent density, dense volume, and non-dense volume. Linear regression models, adjusted for confounders, were used to evaluate associations between gene expression (linear fold change) and mammographic breast density.

Results: One unit increase in ESR1, RANK, and TNFRSF18 gene expression was associated with 8% (95% CI 0-15%, p value = 0.05), 10% (95% CI 0-20%, p value = 0.04) and % (95% CI 0-9%, p value = 0.04) higher volumetric percent density, respectively. There were no associations between gene expression of other markers and volumetric percent density. One unit increase in osteoprotegerin and PGR gene expression was associated with 12% (95% CI 4-19%, p value = 0.003) and 7% (95% CI 0-13%, p value = 0.04) lower non-dense volume, respectively.

Conclusion: These findings provide new insight on the associations of plasma hormonal and RANK pathway gene expression with mammographic breast density in postmenopausal women and require confirmation in other studies.

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绝经后妇女血浆和乳腺密度中NF-κB （RANK）通路激素和受体激活因子基因表达。

背景：激素影响乳腺组织增殖。研究循环激素水平与乳房x线摄影乳房密度之间的关系报告了相互矛盾的结果。由于研究数量有限，我们研究了绝经后妇女血浆中激素基因表达及其下游介质与乳房x线摄影乳腺密度的关系。方法：我们招募了在圣路易斯华盛顿大学医学院进行年度乳房x光筛查的绝经后妇女。我们使用NanoString nCounter平台定量分析了血浆中激素(催乳素、孕激素受体（PGR）、雌激素受体1 （ESR1）、信号转导和转录激活因子（STAT1和STAT5）以及核因子- kb （RANK）通路标记物（RANK、RANKL、骨保护素、TNFRSF18和TNFRSF13B）的基因表达。我们使用Volpara来测量体积百分比密度、密集体积和非密集体积。使用校正混杂因素的线性回归模型来评估基因表达（线性折叠变化）与乳房x线摄影乳腺密度之间的关系。结果：ESR1、RANK和TNFRSF18基因表达增加1个单位分别与体积百分比密度增加8% （95% CI 0-15%， p值= 0.05）、10% （95% CI 0-20%， p值= 0.04）和% （95% CI 0-9%， p值= 0.04）相关。其他标记的基因表达与体积百分比密度无相关性。骨保护素和PGR基因表达每增加一个单位分别与非致密体积降低12% （95% CI 4 ~ 19%， p值= 0.003）和7% （95% CI 0 ~ 13%， p值= 0.04）相关。结论：这些发现为绝经后妇女血浆激素和RANK通路基因表达与乳腺密度的关系提供了新的认识，需要其他研究证实。

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来源期刊

Breast Cancer Research 医学-肿瘤学

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期刊介绍： Breast Cancer Research is an international, peer-reviewed online journal, publishing original research, reviews, editorials and reports. Open access research articles of exceptional interest are published in all areas of biology and medicine relevant to breast cancer, including normal mammary gland biology, with special emphasis on the genetic, biochemical, and cellular basis of breast cancer. In addition to basic research, the journal publishes preclinical, translational and clinical studies with a biological basis, including Phase I and Phase II trials.