Journal
ONCOTARGET
Volume 7, Issue 33, Pages 53102-53115Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.10632
Keywords
uterine aspirate; endometrial cancer; biomarker verification; high resolution accurate mass spectrometry; parallel reaction monitoring
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Funding
- Spanish Ministry of Health [RD12/0036/0035]
- Spanish Ministry of Economy and Competitivity (Juan de la Cierva - Formacion) [PI14/02043, FPDI-2013-18322]
- FPU grant from the Spanish Ministry of Education, Culture and Sport [AP2012-5571]
- Fondo Europeo de Desarrollo Regional FEDER [RTC-2014-3110-1]
- AECC (Grupos Estables de Investigacion) [AECC- GCB 110333 REVE]
- Fundacio La Marato TV3 [2/C/2013]
- CIRIT Generalitat de Catalunya [2014 SGR 1330]
- European Commission, 7th Framework Programe, IRSES (PROTBIOFLUID) - Belgium [269285]
- Fonds National de la Recherche du Luxembourg (FNR) via the PEARL-CPIL program
- AFR [6835664, PDR 2013-2]
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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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