Novel Single-Chain Antibody GD3A10 Defines a Chondroitin Sulfate Biomarker for Ovarian Cancer

Abstract

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.

Keywords::

• biomarker
• chondroitin sulfate
• glycosaminoglycans
• ovarian cancer
• phage display antibodies

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.