Development of a sequential workflow based on LC-PRM for the verification of endometrial cancer protein biomarkers in uterine aspirate samples
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Elena Martinez-Garcia1, Antoine Lesur2, Laura Devis1, Alexandre Campos3, Silvia Cabrera4, Jan van Oostrum2, Xavier Matias-Guiu5, Antonio Gil-Moreno1,4, Jaume Reventos1,6,*, Eva Colas1,5,*, Bruno Domon2,*
1Biomedical Research Group in Gynecology, Vall Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain
2Luxembourg Clinical Proteomics Center (LCP), Luxembourg Institute of Health (LIH), Strassen, Luxembourg
3Sanford-Burnham Medical Research Institute, La Jolla, California, USA
4Gynecological Oncology Department, Vall Hebron University Hospital, Barcelona, Spain
5Pathological Oncology Group and Pathology Department, Hospital Arnau de Vilanova, Lleida, Spain
6Basic Sciences Department, International University of Catalonia, Barcelona, Spain
*These authors have contributed equally and share senior authorship
Eva Colas, email: firstname.lastname@example.org
Bruno Domon, email: email@example.com
Keywords: uterine aspirate, endometrial cancer, biomarker verification, high resolution accurate mass spectrometry, parallel reaction monitoring
Received: April 20, 2016 Accepted: June 07, 2016 Published: July 16, 2016
About 30% of endometrial cancer (EC) patients are diagnosed at an advanced stage of the disease, which is associated with a drastic decrease in the 5-year survival rate. The identification of biomarkers in uterine aspirate samples, which are collected by a minimally invasive procedure, would improve early diagnosis of EC. We present a sequential workflow to select from a list of potential EC biomarkers, those which are the most promising to enter a validation study. After the elimination of confounding contributions by residual blood proteins, 52 potential biomarkers were analyzed in uterine aspirates from 20 EC patients and 18 non-EC controls by a high-resolution accurate mass spectrometer operated in parallel reaction monitoring mode. The differential abundance of 26 biomarkers was observed, and among them ten proteins showed a high sensitivity and specificity (AUC > 0.9). The study demonstrates that uterine aspirates are valuable samples for EC protein biomarkers screening. It also illustrates the importance of a biomarker verification phase to fill the gap between discovery and validation studies and highlights the benefits of high resolution mass spectrometry for this purpose. The proteins verified in this study have an increased likelihood to become a clinical assay after a subsequent validation phase.
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