MUC1 and glycan probing of CA19-9 captured biomarkers from cyst fluids and serum provides enhanced recognition of ovarian cancer

Abstract Glycosylation changes of circulating proteins carrying the CA19-9 antigen may offer new targets for detection methods to be explored for the diagnosis of epithelial ovarian cancer (EOC). Search for assay designs for targets initially captured by a CA19-9 antigen reactive antibody from human...

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Main Authors: Shamima Afrin Ruma, Rufus Vinod, Shruti Jain, Kaisa Huhtinen, Johanna Hynninen, Janne Leivo, Kim Pettersson, Karin Sundfeldt, Kamlesh Gidwani
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-86735-z
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author Shamima Afrin Ruma
Rufus Vinod
Shruti Jain
Kaisa Huhtinen
Johanna Hynninen
Janne Leivo
Kim Pettersson
Karin Sundfeldt
Kamlesh Gidwani
author_facet Shamima Afrin Ruma
Rufus Vinod
Shruti Jain
Kaisa Huhtinen
Johanna Hynninen
Janne Leivo
Kim Pettersson
Karin Sundfeldt
Kamlesh Gidwani
author_sort Shamima Afrin Ruma
collection DOAJ
description Abstract Glycosylation changes of circulating proteins carrying the CA19-9 antigen may offer new targets for detection methods to be explored for the diagnosis of epithelial ovarian cancer (EOC). Search for assay designs for targets initially captured by a CA19-9 antigen reactive antibody from human body fluids by probing with fluorescent nanoparticles coated with lectins or antibodies to known EOC associated proteins. CA19-9 antigens were immobilized from ascites fluids, ovarian cyst fluids or serum samples using monoclonal antibody C192 followed by probing of carrier proteins using anti-MUC16, anti-MUC1 and, anti STn antibodies and seven lectins, all separately coated on nanoparticles. Compared to reference CA19-9 and CA125 immunoassays, nanoparticle aided detection using MUC16, Ma695 and STn antibodies and lectin WGA provided, both separately and combined, improved discrimination of EOC and borderline cancers from benign samples when applied to 60 cyst fluid specimens. When applied to a panel of 44 serum samples (EOC N = 24, healthy and benign samples N = 20) two assays, CA19-9Ma695 and CA19-9MUC1, stood out with equally superior separations (p-values < 10–8) of the two groups compared to conventional CA19-9 immunoassay (p-value 0.03).Eu+3 -NP based CA19-9MUC16, CA19-9Ma695, CA19-9STn and CA19-9WGA show promise for improved EOC detection when applied to ascites & cyst fluids. When applied to circulation-derived samples, the two MUC1 based assays, CA19-9Ma695 and CA19-9Ma552 outperformed other assay constructs. Our results call for further validation in larger EOC cohorts preferentially with early stage ovarian cancers and all major histotypes against commonly occurring benign conditions.
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spelling doaj-art-2dc107e50e124c669793486cef89ce162025-01-26T12:24:36ZengNature PortfolioScientific Reports2045-23222025-01-011511910.1038/s41598-025-86735-zMUC1 and glycan probing of CA19-9 captured biomarkers from cyst fluids and serum provides enhanced recognition of ovarian cancerShamima Afrin Ruma0Rufus Vinod1Shruti Jain2Kaisa Huhtinen3Johanna Hynninen4Janne Leivo5Kim Pettersson6Karin Sundfeldt7Kamlesh Gidwani8Department of Life Technologies, Division of Biotechnology, University of TurkuDepartment of Life Technologies, Division of Biotechnology, University of TurkuDepartment of Life Technologies, Division of Biotechnology, University of TurkuInstitute of Biomedicine and FICAN West Cancer Centre, University of Turku and Turku University HospitalInstitute of Biomedicine and FICAN West Cancer Centre, University of Turku and Turku University HospitalDepartment of Life Technologies, Division of Biotechnology, University of TurkuDepartment of Life Technologies, Division of Biotechnology, University of TurkuDepartment of Obstetrics and Gynecology, Institute of Clinical Sciences, Sahlgrenska Center for Cancer Research, University of GothenburgDepartment of Life Technologies, Division of Biotechnology, University of TurkuAbstract Glycosylation changes of circulating proteins carrying the CA19-9 antigen may offer new targets for detection methods to be explored for the diagnosis of epithelial ovarian cancer (EOC). Search for assay designs for targets initially captured by a CA19-9 antigen reactive antibody from human body fluids by probing with fluorescent nanoparticles coated with lectins or antibodies to known EOC associated proteins. CA19-9 antigens were immobilized from ascites fluids, ovarian cyst fluids or serum samples using monoclonal antibody C192 followed by probing of carrier proteins using anti-MUC16, anti-MUC1 and, anti STn antibodies and seven lectins, all separately coated on nanoparticles. Compared to reference CA19-9 and CA125 immunoassays, nanoparticle aided detection using MUC16, Ma695 and STn antibodies and lectin WGA provided, both separately and combined, improved discrimination of EOC and borderline cancers from benign samples when applied to 60 cyst fluid specimens. When applied to a panel of 44 serum samples (EOC N = 24, healthy and benign samples N = 20) two assays, CA19-9Ma695 and CA19-9MUC1, stood out with equally superior separations (p-values < 10–8) of the two groups compared to conventional CA19-9 immunoassay (p-value 0.03).Eu+3 -NP based CA19-9MUC16, CA19-9Ma695, CA19-9STn and CA19-9WGA show promise for improved EOC detection when applied to ascites & cyst fluids. When applied to circulation-derived samples, the two MUC1 based assays, CA19-9Ma695 and CA19-9Ma552 outperformed other assay constructs. Our results call for further validation in larger EOC cohorts preferentially with early stage ovarian cancers and all major histotypes against commonly occurring benign conditions.https://doi.org/10.1038/s41598-025-86735-zCA19-9MUC1MUC16Europium nanoparticlesEpithelial ovarian cancerCYST fluids
spellingShingle Shamima Afrin Ruma
Rufus Vinod
Shruti Jain
Kaisa Huhtinen
Johanna Hynninen
Janne Leivo
Kim Pettersson
Karin Sundfeldt
Kamlesh Gidwani
MUC1 and glycan probing of CA19-9 captured biomarkers from cyst fluids and serum provides enhanced recognition of ovarian cancer
Scientific Reports
CA19-9
MUC1
MUC16
Europium nanoparticles
Epithelial ovarian cancer
CYST fluids
title MUC1 and glycan probing of CA19-9 captured biomarkers from cyst fluids and serum provides enhanced recognition of ovarian cancer
title_full MUC1 and glycan probing of CA19-9 captured biomarkers from cyst fluids and serum provides enhanced recognition of ovarian cancer
title_fullStr MUC1 and glycan probing of CA19-9 captured biomarkers from cyst fluids and serum provides enhanced recognition of ovarian cancer
title_full_unstemmed MUC1 and glycan probing of CA19-9 captured biomarkers from cyst fluids and serum provides enhanced recognition of ovarian cancer
title_short MUC1 and glycan probing of CA19-9 captured biomarkers from cyst fluids and serum provides enhanced recognition of ovarian cancer
title_sort muc1 and glycan probing of ca19 9 captured biomarkers from cyst fluids and serum provides enhanced recognition of ovarian cancer
topic CA19-9
MUC1
MUC16
Europium nanoparticles
Epithelial ovarian cancer
CYST fluids
url https://doi.org/10.1038/s41598-025-86735-z
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