ArticleCellular oncology (Dordrecht, Netherlands)2021
The changing microRNA landscape by color and cloudiness: a cautionary tale for nipple aspirate fluid biomarker analysis.
Article in Cellular oncology (Dordrecht, Netherlands), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 7 citations in OpenAlex.
- Extracellular vesicles in nipple discharge for breast cancer screening.Breast cancer research and treatment · 2026Article
- Nipple aspirate fluid as a proximal breast liquid biopsy platform: advancing precision risk management in breast cancer.Clinical proteomics · 2026Review
- Quantification of EV-associated miRNA in liquid biopsies for biomarker signature development.Extracellular vesicles and circulating nucleic acids · 2026Review
- The Diagnostic Value of microRNA Expression Analysis in Detecting Intraductal Papillomas in Patients with Pathological Nipple Discharge.International journal of molecular sciences · 2024Article
- Elevated miR-29c-5p Expression in Nipple Aspirate Fluid Is Associated with Extremely High Mammographic Breast Density.Cancers · 2022Article
- Patient-centered research: how do women tolerate nipple fluid aspiration as a potential screening tool for breast cancer?BMC cancer · 2022Article
- Nipple Aspirate Fluid at a Glance.Cancers · 2021Review
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
purposeInvestigation of nipple aspirate fluid (NAF)-based microRNAs (miRNAs) as a potential screening tool for women at increased risk of developing breast cancer is the scope of our research. While aiming to identify discriminating NAF-miRNAs between women with different mammographic densities, we were confronted with an unexpected confounder: NAF sample appearance. Here we report and alert for the impact of NAF color and cloudiness on miRNA assessment.
methodsSeven classes of NAF colors coupled with cloudiness appearance were established. Using 173 NAF samples from 154 healthy women (19 samples were bilaterally collected), the expression of 14 target and 2 candidate endogenous control (EC) miRNAs was investigated using Taqman Advanced miRNA assays to identify significant differential expression patterns between color-cloudiness classes. Inter- and intra-individual variation of miRNA expression was analyzed using the coefficient of variation (CV).
resultsWe found that between the seven NAF classes, fold change miRNA expression differences ranged between 2.4 and 19.6 depending on the interrogated miRNA. Clear NAF samples exhibited higher miRNA expression levels compared to cloudy NAF samples with fold change differences ranging between 1.1 and 6.2. Inter-individual and intra-individual miRNA expression was fairly stable (CV < 15 %), but nevertheless impacted by NAF sample appearance. Within NAF classes, inter-individual variation was largest for green samples (CV 6-15 %) and smallest for bloody samples (CV 2-6 %).
conclusionsOur data indicate that NAF color and cloudiness influence miRNA expression and should, therefore, be systematically registered using an objective color classification system. Given that sample appearance is an inherent feature of NAF, these variables should be statistically controlled for in multivariate data analyses. This cautionary note and recommendations could be of value beyond the field of NAF-miRNAs, given that variability in sample color and cloudiness is likewise observed in liquid biopsies such as urine, cerebrospinal fluid and sputum, and could thereby influence the levels of miRNAs and other biomarkers.
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