Shotgun proteomics coupled to nanoparticle-based biomarker enrichment reveals a novel panel of extracellular matrix prot
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RESEARCH ARTICLE
Open Access
Shotgun proteomics coupled to nanoparticle-based biomarker enrichment reveals a novel panel of extracellular matrix proteins as candidate serum protein biomarkers for early-stage breast cancer detection Claudia Fredolini1, Khyatiben V. Pathak2, Luisa Paris1, Kristina M. Chapple2, Kristine A. Tsantilas2, Matthew Rosenow2, Tony J. Tegeler2, Krystine Garcia-Mansfield2, Davide Tamburro1, Weidong Zhou1, Paul Russo1, Samuele Massarut3, Francesco Facchiano4, Claudio Belluco3, Ruggero De Maria5,6, Enrico Garaci7, Lance Liotta1, Emanuel F. Petricoin1 and Patrick Pirrotte2*
Abstract Background: The lack of specificity and high degree of false positive and false negative rates when using mammographic screening for detecting early-stage breast cancer is a critical issue. Blood-based molecular assays that could be used in adjunct with mammography for increased specificity and sensitivity could have profound clinical impact. Our objective was to discover and independently verify a panel of candidate blood-based biomarkers that could identify the earliest stages of breast cancer and complement current mammographic screening approaches. Methods: We used affinity hydrogel nanoparticles coupled with LC-MS/MS analysis to enrich and analyze lowabundance proteins in serum samples from 20 patients with invasive ductal carcinoma (IDC) breast cancer and 20 female control individuals with positive mammograms and benign pathology at biopsy. We compared these results to those obtained from five cohorts of individuals diagnosed with cancer in organs other than breast (ovarian, lung, prostate, and colon cancer, as well as melanoma) to establish IDC-specific protein signatures. Twenty-four IDC candidate biomarkers were then verified by multiple reaction monitoring (LC-MRM) in an independent validation cohort of 60 serum samples specifically including earliest-stage breast cancer and benign controls (19 early-stage (T1a) IDC and 41 controls). (Continued on next page)
* Correspondence: [email protected] 2 Collaborative Center for Translational Mass Spectrometry, Translational Genomics Research Institute, 445 N 5th St, Phoenix, AZ 85004, USA Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licen
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