Glycans are important partners in many biological processes, including carcinogenesis. The rapidly developing field of functional glycomics becomes one of the frontiers of biology and biomedicine. Aberrant glycosylation of proteins and lipids occurs commonly during malignant transformation and leads to the expression of specific tumor-associated glycans. The appearance of aberrant glycans on carcinoma cells is typically associated with grade, invasion, metastasis and overall poor prognosis. Cancer-associated carbohydrates are mostly located on the surface of cancer cells and are therefore potential diagnostic biomarkers. Currently, there is increasing interest in cancer-associated aberrant glycosylation, with growing numbers of characteristic cancer targets being detected every day. Breast and ovarian cancer are the most common and lethal malignancies in women, respectively, and potential glycan biomarkers hold promise for early detection and targeted therapies. However, the acceleration of research and comprehensive multi-target investigation of cancer-specific glycans could only be successfully achieved with the help of a combination of novel high-throughput glycomic approaches.
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. 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. We 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. Our 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.