Development of a sequential workflow based on LC-PRM for the verification of endometrial cancer protein biomarkers in uterine aspirate samples
Martinez-Garcia, Elena (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Lesur, Antoine (Luxembourg Clinical Proteomics Center (LCP), Luxembourg Institute of Health (LIH), Strassen, Luxembourg)
Devis Jauregui, Laura (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Campos, Alexandre (Sanford-Burnham Medical Research Institute, La Jolla, California, USA)
Cabrera Díaz, Silvia (Hospital Universitari Vall d'Hebron)
van Oostrum, Jan (Luxembourg Clinical Proteomics Center (LCP), Luxembourg Institute of Health (LIH), Strassen, Luxembourg)
Matias-Guiu, Xavier (Hospital Arnau de Vilanova (Lleida, Catalunya))
Gil-Moreno, Antonio 1965- (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Reventos, Jaume (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Colás Ortega, Eva (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Domon, Bruno (Luxembourg Clinical Proteomics Center (LCP), Luxembourg Institute of Health (LIH), Strassen, Luxembourg)
Universitat Autònoma de Barcelona

Data:	2016
Resum:	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.
Ajuts:	Ministerio de Economía y Competitividad PI14-0204 Ministerio de Economía y Competitividad FPDI-2013-18322 Ministerio de Educación, Cultura y Deporte AP2012-5571 Agència de Gestió d'Ajuts Universitaris i de Recerca 2014-SGR-1330 European Commission 269285
Nota:	Altres ajuts: The present work has been also funded by the "Fonds National de la Recherche du Luxembourg" (FNR) via the PEARL-CPIL program to BD, and an AFR grant to AL (PDR 2013-2, Project Reference 6835664). The authors would like to acknowledge the work of all clinicians that have participated in the recruitment of clinical samples. We thank the patients for their willingness to participate in the study.
Nota:	Altres ajuts: FEDER/RTC-2014-3110-1
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Uterine aspirate ; Endometrial cancer ; Biomarker verification ; High resolution accurate mass spectrometry ; Parallel reaction monitoring
Publicat a:	Oncotarget, Vol. 7 (july 2016) , p. 53102-53115, ISSN 1949-2553

DOI: 10.18632/oncotarget.10632
PMID: 27447978

14 p, 5.6 MB

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