title: Development of a sequential workflow based on LC-PRM for the verification of endometrial cancer protein biomarkers in uterine aspirate samples.
abstract: 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.
authors.affiliation: Biomedical Research Group in Gynecology, Vall Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Martinez-Garcia
authors.affiliation: Luxembourg Clinical Proteomics Center (LCP), Luxembourg Institute of Health (LIH), Strassen, Luxembourg.
authors.forename: Antoine
authors.initials: A
authors.lastname: Lesur
authors.affiliation: Biomedical Research Group in Gynecology, Vall Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Devis
authors.affiliation: Sanford-Burnham Medical Research Institute, La Jolla, California, USA.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Campos
authors.affiliation: Gynecological Oncology Department, Vall Hebron University Hospital, Barcelona, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Cabrera
authors.affiliation: Luxembourg Clinical Proteomics Center (LCP), Luxembourg Institute of Health (LIH), Strassen, Luxembourg.
authors.forename: Jan
authors.initials: J
authors.lastname: van Oostrum
authors.affiliation: Pathological Oncology Group and Pathology Department, Hospital Arnau de Vilanova, Lleida, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Matias-Guiu
authors.affiliation: Biomedical Research Group in Gynecology, Vall Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain.|Gynecological Oncology Department, Vall Hebron University Hospital, Barcelona, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Gil-Moreno
authors.affiliation: Biomedical Research Group in Gynecology, Vall Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain.|Basic Sciences Department, International University of Catalonia, Barcelona, Spain.
authors.forename: Jaume
authors.initials: J
authors.lastname: Reventos
authors.affiliation: Biomedical Research Group in Gynecology, Vall Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain.|Pathological Oncology Group and Pathology Department, Hospital Arnau de Vilanova, Lleida, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Colas
authors.affiliation: Luxembourg Clinical Proteomics Center (LCP), Luxembourg Institute of Health (LIH), Strassen, Luxembourg.
authors.forename: Bruno
authors.initials: B
authors.lastname: Domon
mesh_terms: D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001707:Biopsy, Needle; D016889:Endometrial Neoplasms / Q000378:metabolism* / Q000473:pathology; D004717:Endometrium / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D040901:Proteomics / Q000379:methods; D015203:Reproducibility of Results; D012107:Research Design; D014599:Uterus / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor
keywords: biomarker verification; endometrial cancer; high resolution accurate mass spectrometry; parallel reaction monitoring; uterine aspirate