Highly sulfated chondroitin sulfates, a novel class of prognostic biomarkers in ovarian cancer tissue

ObjectiveClinical decision making in ovarian cancer needs new (prognostic) biomarkers. Although the search for biomarkers has traditionally focused on tumor cells, their surrounding contains important information as well. Glycosaminoglycans, heterogeneous polysaccharides which are abundantly present in the stromal compartment, are indicated in several pathological processes including cancer. In this study we investigated a specific glycosaminoglycan motif (4,6-disulfated chondroitin sulfate) for its potential as a prognostic biomarker in ovarian cancer.Methods4,6-Disulfated chondroitin sulfate presence was studied immunohistochemically using the single chain antibody GD3G7 on 148 ovarian tumors including benign and malignant tumors, and tumors with low malignant potential. For comparative purposes p53 and Ki-67 were evaluated. X2 tests, univariate and multivariate Cox proportional hazards analyses were applied for statistical analysis.ResultsThe stroma of malignant tumors showed significantly increased expression of 4,6-disulfated chondroitin sulfate (GD3G7 epitope) compared with benign tumors and tumors with LMP (p-values < 0.000 and 0.002, respectively). Expression of GD3G7 in malignant tumors was significantly correlated with serous subtype, high tumor grade, advanced FIGO-stage and high CA-125 levels. In patients with advanced FIGO stage GD3G7 expression was significantly correlated with incomplete debulking and good response to platinum-based chemotherapy. GD3G7 surpassed both p53 and Ki-67 in statistical analysis. Multivariate survival analysis revealed GD3G7 expression as an independent predictor for progression free survival.ConclusionGlycosaminoglycan motifs may form a new class of biomarkers for (ovarian) cancer, as indicated here for the GD3G7 epitope. Expression of GD3G7 may contribute in therapeutic decision making and constitutes a potential biomarker for poor prognosis.

► Tumor-related alterations in the extracellular matrix, regarding chondroitin sulfate motifs, are proposed as a novel biomarker in ovarian cancer.
► A significant increase of 4,6-disulfated chondroitin sulfate (defined by antibody GD3G7) was observed in malignant ovarian tumors.
► GD3G7 expression correlates with survival and prognostic clinical parameters including advanced FIGO stage (III–IV), chemotherapeutic response and tumor resectability.