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Title: Detection of glyco-mucin profiles improves specificity of MUC16 and MUC1 biomarkers in ovarian serous tumours
Author: Ricardo, Sara
Marcos-Silva, Lara
Pereira, Daniela
Pinto, Rita
Almeida, Raquel
Söderberg, Ola
Mandel, Ulla
Clausen, Henrik
Felix, Ana
Lunet, Nuno
David, Leonor
Keywords: Glyco-mucin profile
Ovarian cancer
Proximity ligation assay
Molecular Medicine
Cancer Research
Issue Date: 1-Feb-2015
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.
Description: Support by Programa Operacional Ciencia e Inovacao 2010 do Quadro Comunitario de Apoio III and FEDER (PTDC/SAU-ONC/117216/2010). IPATIMUP is an Associate Laboratory of the Portuguese Ministry of Science, Technology and Higher Education and partially supported by FCT. Project NORTE - 07-0124-FEDER-000024 co-financed by Programa Operacional Regional do Norte (ON.2 - O Novo Norte), under Quadro de Referencia Estrategico Nacional (QREN), by Fundo Europeu de Desenvolvimento Regional (FEDER). Lara Marcos-Silva acknowledges also FCT for financial support through a PhD fellowship (SFRH/BD/60536/2009). Support by Kirsten og Freddy Johansen Fonden, A.P. Moller og Hustru Chastine McKinney Mollers Fond til Almene Formaal, The Novo Nordisk Foundation, The Danish Research Councils, a programme of excellence from the University of Copenhagen, and The Danish National Research Foundation (DNRF107).
Peer review: yes
ISSN: 1574-7891
Appears in Collections:NMS-FCM: CEDOC - Artigos em revista internacional com arbitragem científica

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