title: Detection of glyco-mucin profiles improves specificity of MUC16 and MUC1 biomarkers in ovarian serous tumours.
abstract: The CA125 assay detects circulating MUC16 and is one of the most widely used cancer biomarkers for the follow-up of ovarian cancer. We previously demonstrated that detection of aberrant cancer-associated glycoforms of MUC16 as well as MUC1 in circulation could improve the yield of these serum assays. Our aim was to refine ovarian cancer biomarkers by detection of aberrant glycoforms (Tn, STn, and T) of MUC16 and MUC1 in ovarian cancer tissue using Proximity Ligation Assays (PLA). We studied two series of serous ovarian tumours, a pilot series of 66 ovarian tumours (27 cystadenomas, 16 borderline tumours and 23 adenocarcinomas) from Centro Hospitalar S. João, Porto and a validation series of 89 ovarian tumours (17 cystadenomas, 25 borderline tumours and 47 adenocarcinomas) from the Portuguese Institute of Oncology Francisco Gentil, Lisbon. PLA reactions for MUC16/Tn, MUC16/STn, MUC1/Tn and MUC1/STn were negative in benign lesions but often positive in borderline and malignant lesions, in both series. An even better yield was obtained based on positivity for any of the four glyco-mucin profiles, further increasing sensitivity to 72% and 83% in the two series, respectively, with 100% specificity. The strategy is designated glyco-mucin profiling and provides strong support for development of PLA-based serum assays for early diagnosis.
authors.affiliation: IPATIMUP, Institute of Molecular Pathology and Immunology of The University of Porto, Portugal.
authors.forename: Sara
authors.initials: S
authors.lastname: Ricardo
authors.affiliation: IPATIMUP, Institute of Molecular Pathology and Immunology of The University of Porto, Portugal; Faculty of Medicine of The University of Porto, Porto, Portugal; Copenhagen Center for Glycomics, Department of Cellular and Molecular Medicine and School of Dentistry, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Lara
authors.initials: L
authors.lastname: Marcos-Silva
authors.affiliation: IPATIMUP, Institute of Molecular Pathology and Immunology of The University of Porto, Portugal.
authors.forename: Daniela
authors.initials: D
authors.lastname: Pereira
authors.affiliation: IPATIMUP, Institute of Molecular Pathology and Immunology of The University of Porto, Portugal.
authors.forename: Rita
authors.initials: R
authors.lastname: Pinto
authors.affiliation: IPATIMUP, Institute of Molecular Pathology and Immunology of The University of Porto, Portugal; Faculty of Medicine of The University of Porto, Porto, Portugal; Department of Biology, Faculty of Sciences of The University of Porto, Porto, Portugal.
authors.forename: Raquel
authors.initials: R
authors.lastname: Almeida
authors.affiliation: Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Biomedical Center, Uppsala University, Uppsala, Sweden.
authors.forename: Ola
authors.initials: O
authors.lastname: Söderberg
authors.affiliation: Copenhagen Center for Glycomics, Department of Cellular and Molecular Medicine and School of Dentistry, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Ulla
authors.initials: U
authors.lastname: Mandel
authors.affiliation: Copenhagen Center for Glycomics, Department of Cellular and Molecular Medicine and School of Dentistry, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Henrik
authors.initials: H
authors.lastname: Clausen
authors.affiliation: Instituto Português de Oncologia de Lisboa, Lisboa, Portugal; Faculdade de Ciências Médicas - CEDOC, Universidade Nova de Lisboa, Lisboa, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Felix
authors.affiliation: Department of Clinical Epidemiology, Predictive Medicine and Public Health, Faculty of Medicine, University of Porto, Porto, Portugal; Institute of Public Health, University of Porto (ISPUP), Porto, Portugal.
authors.forename: Nuno
authors.initials: N
authors.lastname: Lunet
authors.affiliation: IPATIMUP, Institute of Molecular Pathology and Immunology of The University of Porto, Portugal; Faculty of Medicine of The University of Porto, Porto, Portugal. Electronic address: ldavid@ipatimup.pt.
authors.forename: Leonor
authors.initials: L
authors.lastname: David
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018394:CA-125 Antigen / Q000378:metabolism*; D005260:Female; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D018396:Mucin-1 / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D020033:Protein Isoforms / Q000378:metabolism; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; C060192:MUC1 protein, human; C451759:MUC16 protein, human; D008565:Membrane Proteins; D018396:Mucin-1; D020033:Protein Isoforms
keywords: Glyco-mucin profile; MUC1; MUC16; Ovarian cancer; Proximity ligation assay