Identification of hormone-correlated genes as biomarkers for menstrual cycle phases and menopausal status

Gene and protein expression in the breast varies relative to menopausal status (MS) and menstrual phase (MP), but cancer risk biomarker research using archived benign breast samples is usually uninformed by MS-MP data. We hypothesized that gene expression variation relative to ambient hormones can be exploited to develop markers of MS-MP that can be measured directly in breast tissue. Random fine needle aspiration samples from the unaffected breasts of 18 women were utilized for Illumina microarray analysis. Gene expression was correlated with simultaneous serum levels of estradiol, progesterone, and follicle stimulating hormone (FSH). True MS-MP states were defined by age and serum hormones. Genes highly correlated to serum hormones were used to classify samples into 2 MS groups: premenopause or postmenopause. The premenopausal samples were further classified into 3 MP groups: early follicular, late follicular or luteal.

乳腺中的基因与蛋白质表达会随绝经状态（menopausal status, MS）及月经周期阶段（menstrual phase, MP）发生变化，但现有利用存档良性乳腺样本开展的癌症风险生物标志物研究，通常未纳入绝经状态-月经周期阶段（MS-MP）相关数据。本研究假设，与体内激素水平相关的基因表达差异，可用于开发可直接在乳腺组织中检测的MS-MP相关标志物。本研究选取18名女性未受累乳腺的随机细针穿刺抽吸样本，开展Illumina微阵列分析。将基因表达水平与同步检测的血清雌二醇（estradiol）、孕酮（progesterone）及促卵泡激素（follicle stimulating hormone, FSH）水平进行相关性分析。以年龄及血清激素水平作为真实MS-MP状态的判定依据。选取与血清激素水平高度相关的基因，将样本划分为绝经前、绝经后两个MS组，并将绝经前样本进一步划分为早卵泡期、晚卵泡期及黄体期三个MP组。