Abstract
BackgroundGlycosphingolipids are important compounds of the plasma membrane of mammalian cells and a number of them have been associated with malignant transformation and progression, reinforcing tumour aggressiveness and metastasis. Here we investigated the levels of naturally occurring anti-glycan antibodies to Globo H in blood plasma obtained from high-grade serous ovarian cancer patients (SOC) and women without gynaecological malignancies (control) using suspension glycan array technology employing chemically synthesized glycans as antibody targets.ResultsWe found that anti-human Globo H IgG antibodies were able to significantly discriminate SOC from controls (P < 0.05). A combination with the clinically used tumour marker CA125 increased the diagnostic performance (AUC 0.8711). We next compared suspension array with standard flow cytometry in plasma samples and found that the level of anti-Globo H antibodies highly correlated (r = 0.992). The incubation of plasma-derived anti-glycan antibodies with chemically synthesized (presented on fluorescence microspheres) and native Globo H (expressed on Globo H-positive cell lines) revealed strong reactivity of naturally occurring human anti-Globo H antibodies towards its antigen expressed on ovarian cancer cells.ConclusionsOur data demonstrate that human plasma-derived antibodies to Globo H as well as the presence of the antigen might be considered as therapeutic option in ovarian cancer.
Highlights
Glycosphingolipids are important compounds of the plasma membrane of mammalian cells and a number of them have been associated with malignant transformation and progression, reinforcing tumour aggressiveness and metastasis
We investigated the presence of anti-glycan antibodies (AGA) to Globo H in a cohort of 48 blood plasma samples, consisting of high-grade serous ovarian cancer patients (SOC) (n = 19) and a control group (n = 29) comprising women without or benign disease of the gynaecological tract
We performed receiver operating characteristics (ROC) analysis including the current clinical ovarian cancer biomarker CA125, which was measured by ELISA during clinical examinations at initial diagnosis
Summary
Glycosphingolipids are important compounds of the plasma membrane of mammalian cells and a number of them have been associated with malignant transformation and progression, reinforcing tumour aggressiveness and metastasis. Globo H was shown to be an antigen for naturally occurring plasma-derived AGA in breast and some other epithelial cancers with high specificity [20]. These antibodies were assessed by the glycan microarray technology and their levels were significantly different in serum of breast cancer patients and healthy individuals [21]. Despite these few reports, there is limited knowledge on Globo H antigen expression on cell lines and the presence of naturally circulating AGA in plasma from ovarian cancer patients
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