Longitudinal Serum Protein Analysis of Women with a High Risk of Developing Breast Cancer Reveals Large Interpatient Versus Small Intrapatient Variations: First Results from the TESTBREAST Study
Hagenaars, Sophie C; Dekker, Lennard J M; Ravesteijn, Bob; van Vlierberghe, Ronald L P; Romijn, Fred P H T M; Verhoeff, Linda; Witkamp, Arjen J; Schenk, Karin E; Keymeulen, Kristien B I M; Menke-Pluijmers, Marian B E; Dassen, Anneriet E; Kortmann, Birgitta A; de Vries, Jakob; Rutgers, Emiel J T; van der Burgt, Yuri E M; Meershoek-Klein Kranenbarg, Elma; Cobbaert, Christa M; Luider, Theo M; Mesker, Wilma E; Tollenaar, Rob A E M
(2022) International journal of molecular sciences, volume 23, issue 20, pp. 1 - 11
(Article)
Abstract
The prospective, multicenter TESTBREAST study was initiated with the aim of identifying a novel panel of blood-based protein biomarkers to enable early breast cancer detection for moderate-to-high-risk women. Serum samples were collected every (half) year up until diagnosis. Protein levels were longitudinally measured to determine intrapatient and interpatient variabilities. To
... read more
this end, protein cluster patterns were evaluated to form a conceptual basis for further clinical analyses. Using a mass spectrometry-based bottom-up proteomics strategy, the protein abundance of 30 samples was analyzed: five sequential serum samples from six high-risk women; three who developed a breast malignancy (cases) and three who did not (controls). Serum samples were chromatographically fractionated and an in-depth serum proteome was acquired. Cluster analyses were applied to indicate differences between and within protein levels in serum samples of individuals. Statistical analyses were performed using ANOVA to select proteins with a high level of clustering. Cluster analyses on 30 serum samples revealed unique patterns of protein clustering for each patient, indicating a greater interpatient than intrapatient variability in protein levels of the longitudinally acquired samples. Moreover, the most distinctive proteins in the cluster analysis were identified. Strong clustering patterns within longitudinal intrapatient samples have demonstrated the importance of identifying small changes in protein levels for individuals over time. This underlines the significance of longitudinal serum measurements, that patients can serve as their own controls, and the relevance of the current study set-up for early detection. The TESTBREAST study will continue its pursuit toward establishing a protein panel for early breast cancer detection.
show less
Download/Full Text
Keywords: Biomarkers, Biomarkers, Tumor, Blood Proteins/analysis, Breast Neoplasms/pathology, Female, Humans, Prospective Studies, Proteome/metabolism, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods, proteomics, biomarkers, longitudinal analysis, breast cancer, homeostasis, clustering, inter-intra patient variation, early detection, serum, liquid biopsy, Molecular Biology, Spectroscopy, Catalysis, Inorganic Chemistry, Computer Science Applications, Physical and Theoretical Chemistry, Organic Chemistry, Multicenter Study, Journal Article
ISSN: 1422-0067
Publisher: Multidisciplinary Digital Publishing Institute (MDPI)
Note: Funding Information: The TESTBREAST study was supported with research grants from the Bollenstreekfonds Lisse, Pink Ribbon (2011.VW06.C725 or Dutch Cancer Society (KWF) number UL 2016–8172), A Sisters Hope, Zabawas and Nuts-Ohra. Publisher Copyright: © 2022 by the authors.
(Peer reviewed)