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Nipple aspirate fluid-A liquid biopsy for diagnosing breast health
Sadr-Ul Shaheed1, Catherine Tait2, Kyriacos Kyriacou3
1Institute of Cancer Therapeutics, University of Bradford, Bradford, UK.
Insights
Nipple secretions contain numerous proteins, including cancer biomarkers. This study analyzed protein profiles in nipple aspirate fluid (NAF), finding high similarity within patients but significant differences between individuals for potential liquid biopsy applications.
Area of Science:
- Proteomics
- Biomarker Discovery
- Oncology
Background:
- Nipple secretions are protein-rich and a potential source for breast cancer biomarkers.
- Previous studies on specific proteins showed limited correlation with clinicopathological features.
Purpose of the Study:
- To investigate the intra- and interpatient protein composition of nipple secretions.
- To assess the implications of protein profiles for use as liquid biopsies in breast cancer screening.
Main Methods:
- Characterization of matched pairs of nipple discharge/nipple aspirate fluid (NAF) for physicochemical properties and SDS-PAGE.
- Semiquantitative proteomic profiling of NAF using 2D-LC Orbitrap Fusion MS.
- Bioinformatics and statistical evaluation of proteomic data.
Main Results:
- Identification of 1990 unique proteins, including established cancer-associated markers.
- High similarity in protein composition within matched patient pairs (average Pearson correlation coefficient of 0.94).
- Significant variations in protein profiles observed between different individuals.
Conclusions:
- This comprehensive proteomic study of NAF offers a valuable resource for breast cancer biomarker discovery.
- High levels of milk proteins in healthy volunteers, potentially linked to galactorrhoea, were noted.
- Matched pairs enhance confidence in patient-specific protein levels; larger cohorts are needed to investigate cancer stage-related changes.
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.
