Nipple Aspirate Fluid Proteome of Healthy Females and Patients with Breast Cancer

Pavlou, Maria; Kulasingam, Vathany; Sauter, Edward R.; Kliethermes, Beth; Diamandis, Eleftherios P.

doi:10.1373/clinchem.2009.136283

Cited by 40 publications

(34 citation statements)

References 37 publications

(16 reference statements)

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“…Venn diagrams illustrating (C). overlapping identities with the data from the NAF study by Pavlou et al 20, and D. overlapping identities with the Human Plasma Proteome database.…”

Section: Resultsmentioning

confidence: 90%

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Nipple aspirate fluid—A liquid biopsy for diagnosing breast health

Shaheed

Tait

Kyriacou

et al. 2017

Proteomics Clinical Apps

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PurposeNipple 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 designMatched 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.ResultsA 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 relevanceThis 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.

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“…Venn diagrams illustrating (C). overlapping identities with the data from the NAF study by Pavlou et al 20, and D. overlapping identities with the Human Plasma Proteome database.…”

Section: Resultsmentioning

confidence: 90%

“…Prior to this study, the most complete proteomics profile of NAF was that of Pavlou et al. 20. Comparison with our dataset, based on gene identity (691 entries Pavlou et al., and 1919 for our set, excluding immunoglobulin isoforms), indicated an overlap of 563 proteins (Fig.…”

Section: Resultsmentioning

confidence: 99%

Nipple aspirate fluid—A liquid biopsy for diagnosing breast health

Shaheed

Tait

Kyriacou

et al. 2017

Proteomics Clinical Apps

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“…In addition, targeted multiplex mass spectrometry is emerging as a novel quantitative strategy for measuring protein signatures in tumor tissues or blood. Proteomic studies of breast cancer cells and tissues have already shown the potential for candidate biomarkers discovery (17)(18)(19)(20)(21)(22). In a promising pilot study using SELDI-TOF-MS, serum peptide profiles could distinguish women with BRCA1 mutations who developed breast cancer from those who did not (carrier), normal volunteers, and women with sporadic breast cancer with good sensitivity and specificity (23).…”

mentioning

confidence: 99%

Proteomics of Mouse BRCA1-deficient Mammary Tumors Identifies DNA Repair Proteins with Potential Diagnostic and Prognostic Value in Human Breast Cancer

Warmoes

Jaspers

Pham

et al. 2012

Molecular & Cellular Proteomics

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Breast cancer 1, early onset (BRCA1) hereditary breast cancer, a type of cancer with defects in the homologydirected DNA repair pathway, would benefit from the identification of proteins for diagnosis, which might also be of potential use as screening, prognostic, or predictive markers. Sporadic breast cancers with defects in the BRCA1 pathway might also be diagnosed. We employed proteomics based on one-dimensional gel electrophoresis in combination with nano-LC-MS/MS and spectral counting to compare the protein profiles of mammary tumor tissues of genetic mouse models either deficient or proficient in BRCA1. We identified a total of 3,545 proteins, of which 801 were significantly differentially regulated between the BRCA1-deficient and -proficient breast tumors. Pathway and protein complex analysis identified DNA repair and related functions as the major processes associated with the up-regulated proteins in the BRCA1-deficient tumors. In addition, by selecting highly connected nodes, we identified a BRCA1 deficiency signature of 45 proteins that enriches for homology-directed DNA repair deficiency in human gene expression breast cancer data sets. This signature also exhibits prognostic power across multiple data sets, with optimal performance in a data set enriched in tumors deficient in homology-directed DNA repair. In conclusion, by comparing mouse proteomes from BRCA1-proficient and -deficient mammary tumors, we were able to identify several markers associated with BRCA1 deficiency and a prognostic signature for human breast cancer deficient in homologydirected DNA repair. Breast cancer associated with BRCA1 1 mutations accounts for 1-2% of breast cancer cases in the Western world. BRCA1 hereditary breast cancer falls into the molecular subtype of basal-like breast cancer that has a poor prognosis (1). Sporadic basal-like breast tumors represent ϳ10 -15% of all breast carcinomas and comprise many tumors that share key features of BRCA1-associated tumors (2). A major function of BRCA1 is its role in homology-directed double-strand break repair, a DNA repair mechanism that uses the sister chromatid as a template and therefore repairs double-strand breaks in an error-free manner. Deficiencies in homology-directed DNA repair cause high levels of genomic instability that increase the risk of tumorigenesis (3, 4). Nevertheless, BRCA1 pathway dysfunction may provide an opportunity for therapeutic intervention: preclinical models suggest an increased sensitivity to ionizing radiation and DNA (repair)-targeting agents (3). In particular, the use of poly[ADP-ribose] polymerase (PARP) inhibitors holds great promise for clinical application. First results from clinical trials support this therapeutic approach for breast cancer (5). A major clinical challenge remains the identification of patients that are likely to benefit from DNA (repair)-targeting therapy. Global analyses of molecular alterations in sporadic or hereditary breast cancer have mainly used genome and transcriptome profiling methods. These studies yielde...

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“…However, this certainly does not preclude using NAF as a source for protein biomarker discovery efforts. A recent study employed multifractionation strategies prior to peptide analysis on an LTQ Orbitrap mass spectrometer and reported over 800 unique proteins present in NAF (Pavlou et al, 2010). Approximately 40% of these proteins are also found in serum/plasma, and over 50% of them were secreted or of plasma membrane origin.…”

Section: Detection Of Breast Cancer Biomarkers In Nipple Aspirate/ducmentioning

confidence: 99%

Challenges to Developing Proteomic-Based Breast Cancer Diagnostics

Drake

Cazares

Jones

et al. 2011

OMICS: A Journal of Integrative Biology

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Over the past decade, multiple genetic and histological approaches have accelerated development of new breast cancer diagnostics and treatment paradigms. Multiple distinct genetic subtypes of breast cancers have been defined, and this has progressively led toward more personalized medicine in regard to treatment options. There still remains a deficiency in the development of molecular diagnostic assays that can be used for breast cancer detection and pretherapy clinical decisions. In particular, the type of cancer-specific biomarker typified by a serum or tissue-derived protein. Progress in this regard has been minimal, especially in comparison to the rapid advancements in genetic and histological assays for breast cancers. In this review, some potential reasons for this large gap in developing protein biomarkers will be discussed, as well as new strategies for improving these approaches. Improvements in the study design of protein biomarker discovery strategies in relation to the genetic subtypes and histology of breast cancers is also emphasized. The current successes in use of genetic and histological assays for breast cancer diagnostics are summarized, and in that context, the current limitations of the types of breast cancer-related clinical samples available for protein biomarker assay development are discussed. Based on these limitations, research strategies emphasizing identification of glycoprotein biomarkers in blood and MALDI mass spectrometry imaging of tissues are described.

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Nipple Aspirate Fluid Proteome of Healthy Females and Patients with Breast Cancer

Cited by 40 publications

References 37 publications

Nipple aspirate fluid—A liquid biopsy for diagnosing breast health

Nipple aspirate fluid—A liquid biopsy for diagnosing breast health

Proteomics of Mouse BRCA1-deficient Mammary Tumors Identifies DNA Repair Proteins with Potential Diagnostic and Prognostic Value in Human Breast Cancer

Challenges to Developing Proteomic-Based Breast Cancer Diagnostics

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