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Novel single-chain antibody GD3A10 defines a chondroitin sulfate biomarker for ovarian cancer


Aims: Ovarian cancer has the highest case-to-fatality-index of all gynecological cancers. In this study, tumor-related alterations in the extracellular matrix, especially regarding chondroitin sulfate glycosaminoglycans, are proposed as a novel biomarker in ovarian cancer. Materials & methods: Phage display technology was applied to select antibody GD3A10, which was obtained by biopanning using embryonic glycosaminoglycans as a source for carcinogenic antigens. GD3A10 antigen specificity was studied in situ using glycosaminoglycan degrading enzymes. A patient cohort (n = 159) was immunohistochemically stained. Scoring was correlated with clinical prognostic parameters and survival. Normal rat organs were used to study normal antigen distribution. Results: GD3A10 is a specific anti-chondroitin sulfate antibody and the epitope was absent or very restricted in normal rat organs, normal ovaries and benign ovarian tumors. Strong stromal expression was observed in malignant ovarian tumors, and correlated with poor prognostic factors such as subtype, tumor grade and recurrence. Conclusion: tumor-associated glycosaminoglycans are an interesting source of biomarkers in ovarian cancer, as shown here using chondroitin sulfate antibody GD3A10.

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