Abstract
Background: Early detection of breast cancer (BC) is critical for increasing survival rates. However, current imaging approaches can provide ambiguous results, requiring invasive tissue biopsy for a definitive diagnosis. Multi-dimensional mass spectrometric analysis has highlighted the invaluable potential of nipple aspirate fluid (NAF) as a non-invasive source of early detection biomarkers, by identifying a multitude of proteins representative of the changing breast microenvironment. However, technical challenges with biomarker validation in large cohorts remain due to low sample throughput, impeding progress towards clinical utility. Rather, by employing a high-throughput method, that is more practicable for clinical utility, perturbations of the most abundant NAF proteins in BC patients compared with non-cancer (NC) controls could be monitored and validated in larger groups. Method: We characterized matched NAF pairs from BC (n = 9) and NC (n = 4) volunteers, using a rapid one dimensional liquid chromatography-mass spectrometry (1D LC-MS/MS) approach. Results: Overall, 198 proteins were relatively quantified, of which 40 were significantly differentiated in BC samples, compared with NC (p ≤ 0.05), with 26 upregulated and 14 downregulated. An imbalance in immune response and proteins regulating cell growth, maintenance and communication were identified. Conclusions: Our findings show 1D LC-MS/MS can quantify changes reflected in the NAF proteome associated with breast cancer development.
Highlights
Breast cancer (BC) is the most common cancer diagnosed among women worldwide and impacts 2.1 million females each year
The color and consistency of nipple aspirate fluid (NAF) varied amongst individuals, and between breasts of a matched pair (Table 1), as did their overall protein profiles indicated by SDS-PAGE (Supplementary Figure S1)
The original proteomics approach was time-consuming and in order to validate biomarkers linked to breast cancer, a more rapid method is required for clinical trials recruiting larger cohorts
Summary
Breast cancer (BC) is the most common cancer diagnosed among women worldwide and impacts 2.1 million females each year. Individuals diagnosed at an advanced stage have a significantly reduced five-year survival rate, ranging from 10–50%, as compared with the significantly higher survival rate for earlier detected, more localized tumors, at approximately 90% [2,3] These trends may reflect the availability of national screening programs, later diagnosis, and poor access to treatment in some countries, and importantly highlight breast cancer as a tremendous public health problem. As an independent diagnostic tool for early-stage disease or aggressive malignancies, imaging techniques are generally limited as they have a reduced threshold of detection in dense breasts and are less sensitive to small tumors [7] Efforts to improve such limitations, with the development of digital breast tomosynthesis, have shown to reduce the number of benign biopsies performed at screening assessment. Conclusions: Our findings show 1D LC-MS/MS can quantify changes reflected in the NAF proteome associated with breast cancer development
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