Methods for identification of CA125 from ovarian cancer ascites by high resolution mass spectrometry

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dc.contributor.authorWeiland, F.
dc.contributor.authorFritz, K.
dc.contributor.authorOehler, M.
dc.contributor.authorHoffmann, P.
dc.date.issued2012
dc.description.abstractCA125 is the most widely used tumour marker in ovarian cancer with unsatisfactory sensitivity and specificity especially at early stage. It is quantified by antibody-based immunoassays; however different molecular weight isoforms have been described in the literature which have never been validated by mass spectrometry, potentially affecting the diagnostic accuracy and clinical reliability of the test. In this study, CA125 was detected by Western blot and its identity confirmed by mass spectrometry. Two-dimensional (2D) gel electrophoresis in combination with mass spectrometry revealed that positive Western blot signals up to 500 kDa are most likely false-positive interactions of M11-like and OC125-like antibodies. Fibronectin, identified as one of these false-positive interaction partners, increased the reading for CA125 in a first generation ELISA significantly (p = 0.02). The existence of low-molecular weight isoforms of CA125 is therefore questionable and is most likely reflecting cross-reactivity of the antibodies with other proteins. This would explain the conflicting reports on the molecular structure of CA125 and also the inconsistency of CA125 levels by different ELISAs. Our results are also the first steps towards a mass spectrometric assay for CA125 quantification, which would improve sensitivity and reliability.
dc.description.statementofresponsibilityFlorian Weiland, Katarina Fritz, Martin K. Oehler and Peter Hoffmann
dc.identifier.citationInternational Journal of Molecular Sciences, 2012; 13(8):9942-9958
dc.identifier.doi10.3390/ijms13089942
dc.identifier.issn1661-6596
dc.identifier.issn1422-0067
dc.identifier.orcidWeiland, F. [0000-0001-9702-9245]
dc.identifier.orcidOehler, M. [0000-0002-2651-5913]
dc.identifier.urihttp://hdl.handle.net/2440/73610
dc.language.isoen
dc.publisherMDPI AG
dc.rights© 2012 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/)
dc.source.urihttps://doi.org/10.3390/ijms13089942
dc.subjectCA125
dc.subjectmucin 16
dc.subjectmass spectrometry
dc.subjectovarian cancer
dc.subjectantibody
dc.subjectfalse-positives
dc.titleMethods for identification of CA125 from ovarian cancer ascites by high resolution mass spectrometry
dc.typeJournal article
pubs.publication-statusPublished

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