Abstract 517: Anti-glycan IgM and IgG antibodies as new biomarkers for serous ovarian cancers

Abstract

Abstract Introduction: Patients with advanced-stage serous cancers (ovarian, peritoneal and tubal) often develop ascites, a protein-rich fluid within the peritoneal cavity which causes significant morbidity and is associated with a poor prognosis. Aberrant glycosylation is a common feature of these cancers and this may impact on the humoral immune response. We hypothesized that serous cancer patients and healthy women have different profiles of anti-glycan antibodies in plasma and ascites. Method: Matched pairs of plasma and ascites were collected from 11 patients with advanced stage disease. A custom-made printed glycan array (PGA) allowed the simultaneous detection of anti-glycan antibodies (AGAs) to 203 chemically synthesised glycans, including some tumour-associated carbohydrate antigens. Identified candidate AGAs were additionally detected using a suspension array in an independent patient cohort of 230 patients. Candidates were selected by their discriminatory power between cancer and healthy controls. One top candidate was further analyzed for its biological behavior using ovarian cancer cell lines. Results: Using PGA, we detected a multitude of AGAs in both plasma and ascites. Levels of AGAs in serum and ascites correlated independent of ascites volume. Serous cancer patients had significantly different levels of plasma IgM to 31 glycans when compared to plasma of 14 healthy control patients, with IgM levels being lower in the cancer group. Significant differences in IgG plasma levels were found for 4 glycans. The trisaccharide P1, part of the P blood group system, was selected for further analyses. Plasma expression of P1 was found independent of cohort and method used. The human serous ovarian cancer cell line, IGROV1, was shown to express P1 and was subsequently sorted into P1-high, P1-low, and P1-negative subpopulations. We found that IGROV1/P1-expressing cells correlated with faster tumor cell migration and invasion. Treatment with a human anti-P1 IgM (clone P3NIL100) inhibited the proliferation of these tumour cells in vitro. Conclusion: P1 expression can be detected in ovarian cancer patients in independent of cohorts. P1 seems to be involved in cancer migration and invasion, and is therefore a potential target for ovarian cancer diagnosis and therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 517. doi:1538-7445.AM2012-517