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乳头抽吸液——一种用于诊断乳腺健康的液体活检

Nipple aspirate fluid-A liquid biopsy for diagnosing breast health.

作者信息

Shaheed Sadr-Ul, Tait Catherine, Kyriacou Kyriacos, Mullarkey Joanne, Burrill Wayne, Patterson Laurence H, Linforth Richard, Salhab Mohamed, Sutton Chris W

机构信息

Institute of Cancer Therapeutics, University of Bradford, Bradford, UK.

Bradford Teaching Hospitals NHS Trust, Bradford, UK.

出版信息

Proteomics Clin Appl. 2017 Sep;11(9-10). doi: 10.1002/prca.201700015. Epub 2017 Jun 26.

Abstract

PURPOSE

Nipple secretions are protein-rich and a potential source of breast cancer biomarkers for breast cancer screening. Previous studies of specific proteins have shown limited correlation with clinicopathological features. Our aim, in this pilot study, was to investigate the intra- and interpatient protein composition of nipple secretions and the implications for their use as liquid biopsies.

EXPERIMENTAL DESIGN

Matched pairs of nipple discharge/nipple aspirate fluid (NAF, n = 15) were characterized for physicochemical properties and SDS-PAGE. Four pairs were selected for semiquantitative proteomic profiling and trypsin-digested peptides analyzed using 2D-LC Orbitrap Fusion MS. The resulting data were subject to bioinformatics analysis and statistical evaluation for functional significance.

RESULTS

A total of 1990 unique proteins were identified many of which are established cancer-associated markers. Matched pairs shared the greatest similarity (average Pearson correlation coefficient of 0.94), but significant variations between individuals were observed.

CONCLUSIONS AND CLINICAL RELEVANCE

This was the most complete proteomic study of nipple discharge/nipple aspirate fluid to date providing a valuable source for biomarker discovery. The high level of milk proteins in healthy volunteer samples compared to the cancer patients was associated with galactorrhoea. Using matched pairs increased confidence in patient-specific protein levels but changes relating to cancer stage require investigation of a larger cohort.

摘要

目的

乳头分泌物富含蛋白质,是乳腺癌筛查中潜在的乳腺癌生物标志物来源。先前对特定蛋白质的研究表明,其与临床病理特征的相关性有限。在这项初步研究中,我们的目的是调查乳头分泌物的患者内和患者间蛋白质组成及其作为液体活检的意义。

实验设计

对配对的乳头溢液/乳头抽吸液(NAF,n = 15)进行物理化学性质和SDS-PAGE表征。选择四对进行半定量蛋白质组分析,并使用二维液相色谱-轨道阱融合质谱分析胰蛋白酶消化的肽段。对所得数据进行生物信息学分析和功能意义的统计评估。

结果

共鉴定出1990种独特蛋白质,其中许多是已确定的癌症相关标志物。配对样本具有最大的相似性(平均皮尔逊相关系数为0.94),但个体间存在显著差异。

结论与临床意义

这是迄今为止对乳头溢液/乳头抽吸液最完整的蛋白质组学研究,为生物标志物发现提供了宝贵资源。与癌症患者相比,健康志愿者样本中乳蛋白水平较高与溢乳有关。使用配对样本增加了对患者特异性蛋白质水平的可信度,但与癌症分期相关的变化需要对更大队列进行研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36bf/5638085/e62d90468d4c/PRCA-11-na-g001.jpg

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