Detection of glyco‐mucin profiles improves specificity of MUC16 and MUC1 biomarkers in ovarian serous tumours

Molecular Oncology - Tập 9 - Trang 503-512 - 2015
Sara Ricardo1, Lara Marcos-Silva1,2,3, Daniela Pereira1, Rita Pinto1, Raquel Almeida1,2,4, Ola Söderberg5, Ulla Mandel3, Henrik Clausen3, Ana Felix6,7, Nuno Lunet8,9, Leonor David1,2
1IPATIMUP, Institute of Molecular Pathology and Immunology of the University of Porto, Portugal
2Faculty of Medicine of The University of Porto, Porto, Portugal
3Copenhagen Center for Glycomics, Department of Cellular and Molecular Medicine and School of Dentistry, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
4Department of Biology, Faculty of Sciences of the University of Porto, Porto, Portugal
5Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Biomedical Center, Uppsala University, Uppsala, Sweden
6Instituto Português de Oncologia de Lisboa, Lisboa, Portugal
7Faculdade de Ciências Médicas – CEDOC, Universidade Nova de Lisboa, Lisboa, Portugal
8Department of Clinical Epidemiology, Predictive Medicine and Public Health, Faculty of Medicine, University of Porto, Porto, Portugal
9Institute of Public Health – University of Porto (ISPUP), Porto, Portugal

Tóm tắt

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.

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