Tredwell Gregory D, Miller Jessica A, Chow H-H Sherry, Thompson Patricia A, Keun Hector C
Department of Surgery and Cancer, Imperial College London , SW7 2AZ London, United Kingdom.
J Proteome Res. 2014 Feb 7;13(2):883-9. doi: 10.1021/pr400924k. Epub 2014 Jan 7.
Nipple aspirate fluid (NAF) is a noninvasively obtained biofluid from the duct openings of the breast. NAF components are constantly secreted, metabolized, and reabsorbed by the epithelial lining of the lactiferous ducts of the breast. NAF has been studied as a potential breast tissue surrogate for the discovery of novel breast cancer risk, early detection, and treatment response biomarkers. We report the first unsupervised metabolite characterization of nipple aspirate fluid using NMR and GC-MS using convenience samples previously collected from four premenopausal and four postmenopausal women. A total of 38 metabolites were identified using the two analytical techniques, including amino acids, organic acids, fatty acids, and carbohydrates. Analytical reproducibility of metabolites in NAF by GC-MS was high across different extraction and analysis days. Overall, 31 metabolites had a coefficient of variation below 20%. By GC-MS, there were eight metabolites unique to NAF, 19 unique to plasma, and 24 shared metabolites. Correlative analysis of shared metabolites between matched NAF and plasma samples from pre- and postmenopausal women shows almost no correlations, with the exception being lactic acid, which was significantly negatively correlated (R(2) = 0.57; P = 0.03). These results suggest that NAF is metabolically distinct from plasma and that the application of metabolomic strategies may be useful for future studies investigating breast cancer risk and intervention response biomarkers.
乳头抽吸液（NAF）是一种从乳腺导管开口处无创获取的生物流体。NAF的成分由乳腺输乳管的上皮内衬不断分泌、代谢和重吸收。NAF已被作为一种潜在的乳腺组织替代物进行研究，用于发现新的乳腺癌风险、早期检测和治疗反应生物标志物。我们报告了首次使用核磁共振（NMR）和气相色谱 - 质谱联用（GC - MS）对乳头抽吸液进行无监督代谢物表征的研究，使用的是先前从四名绝经前和四名绝经后女性中采集的便利样本。通过这两种分析技术共鉴定出38种代谢物，包括氨基酸、有机酸、脂肪酸和碳水化合物。GC - MS分析NAF中代谢物的重现性在不同的提取和分析日期都很高。总体而言，31种代谢物的变异系数低于20%。通过GC - MS分析，有8种代谢物是NAF特有的，19种是血浆特有的，24种是共享代谢物。对绝经前和绝经后女性匹配的NAF和血浆样本中共享代谢物的相关性分析显示，除乳酸呈显著负相关（R(2) = 0.57；P = 0.03）外，几乎没有相关性。这些结果表明，NAF在代谢上与血浆不同，代谢组学策略的应用可能有助于未来研究乳腺癌风险和干预反应生物标志物。
