title: Mucins MUC16 and MUC1 are major carriers of SLe(a) and SLe(x) in borderline and malignant serous ovarian tumors.
abstract: Mucins are heavily glycosylated proteins overexpressed and associated with truncated or sialylated glycans upon malignant transformation. We previously identified a panel of four glyco-mucin profiles (MUC16/Tn, MUC16/STn, MUC1/Tn, and MUC1/STn) with 100 % specificity and 100 % positive predictive value for detection of borderline/malignant serous tumors of the ovary, using proximity ligation assay (PLA). In the present work, using the same method, we studied other mucin glycosylation profiles that might add relevant information for diagnostic purposes. We used PLA probes to MUC16, MUC1, sialyl Lewis(a) (SLe(a)), and sialyl Lewis(x) (SLe(x)) to study a series of 39 ovarian serous tumors (14 adenocarcinomas, 10 borderline ovarian tumors (BOTs), and 15 cystadenomas). Our results demonstrated that, in adenocarcinomas and BOTs, the major carriers of SLe(a) and SLe(x) are MUC16 and/or MUC1 (100 and 92 % for SLe(a) and 64 and 70 % for SLe(x), respectively). In cystadenomas, SLe(a) and SLe(x) are mainly carried by unidentified proteins (85 and 78 %, respectively). Our study identified, for the first time, the major protein carriers of SLe(a) and SLe(x) in ovarian adenocarcinomas and BOTs, MUC1 and MUC16, and also that distinct unidentified carriers are involved in cystadenomas. These results emphasize the relevance of multiple biomarker recognition provided by multiplex assays, such as PLA, to enhance sensitivity and specificity of serum and tissue assays.
authors.affiliation: IPATIMUP, Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal. sricardo@ipatimup.pt.|Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Júlio Amaral de Carvalho, 45, 4200-135, Porto, Portugal. sricardo@ipatimup.pt.|Faculty of Medicine of the University of Porto, Porto, Portugal. sricardo@ipatimup.pt.
authors.forename: Sara
authors.initials: S
authors.lastname: Ricardo
authors.affiliation: IPATIMUP, Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal.|Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Júlio Amaral de Carvalho, 45, 4200-135, Porto, Portugal.
authors.forename: Lara
authors.initials: L
authors.lastname: Marcos-Silva
authors.affiliation: Faculty of Medicine of the University of Porto, Porto, Portugal.
authors.forename: Cristina
authors.initials: C
authors.lastname: Valente
authors.affiliation: IPATIMUP, Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal.|Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Júlio Amaral de Carvalho, 45, 4200-135, Porto, Portugal.|Faculty of Medicine of the University of Porto, Porto, Portugal.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Coelho
authors.affiliation: Oncology Department of Centro Hospitalar S. João, Porto, Portugal.
authors.forename: Rosa
authors.initials: R
authors.lastname: Gomes
authors.affiliation: IPATIMUP, Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal.|Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Júlio Amaral de Carvalho, 45, 4200-135, Porto, Portugal.|Faculty of Medicine of the University of Porto, Porto, Portugal.
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*; D018395:CA-19-9 Antigen; D000077216:Carcinoma, Ovarian Epithelial; D003537:Cystadenoma / Q000175:diagnosis / Q000378:metabolism; D005260:Female; D006579:Heterozygote; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D018396:Mucin-1 / Q000378:metabolism*; D009375:Neoplasms, Glandular and Epithelial / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D009844:Oligosaccharides / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D000080506:Sialyl Lewis X Antigen
chemical_list: D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; D018395:CA-19-9 Antigen; C060192:MUC1 protein, human; C451759:MUC16 protein, human; D008565:Membrane Proteins; D018396:Mucin-1; D009844:Oligosaccharides; D000080506:Sialyl Lewis X Antigen
keywords: MUC16/1; Ovarian cancer; Proximity ligation assay; SLea; SLex