Identification of Circulating Autoantibodies as Novel Ovarian Cancer Biomarkers
Mairead A Murphy, David J O'Connell, John K O'Brien, Sharon O'Toole, Sara L O'Kane, Cara Martin, Orla Sheils, John J O'Leary, Dolores J Cahill. Trinity College Dublin, Dublin, Ireland; University College Dublin, Dublin, Ireland
Background: Early diagnosis of ovarian cancer (OC) is the most important determinant of survival. However, symptoms of OC are non-specific and there are no reliable biomarkers resulting in the majority of OC diagnosed at late stage. Autoantibodies are an extremely attractive biomarker entity as they are present in blood and easily adapted into current diagnostic platforms. (E.L.I.S.A.) This research aims to determine the utility of autoantibodies as novel OC biomarkers.
Design: Study approval was obtained from SJH/AMNCH research ethics committee. To profile the autoantibody response in patients two different array platforms were used; the Human Expression Library (hEx1) and the Invitrogen Protoarray (n=>10,000 proteins). Benign ovarian disease, early stage ovarian cancer and late stage ovarian cancer patient sera, in addition to Non-Remarkable (Healthy) control subjects were screened. Antigens identified to be associated with these cohorts were interrogated by Western immunoblotting and E.L.I.S.A. Pathway analysis was also performed to identify pathway deregulation associated with malignancy.
Results: Autoantibodies to p53 were identified in patient sera. Western blotting confirmed highly specific OC association, present in 25% (n= 5/25) of late stage OC sera and not present in healthy control sera (n=15). In addition novel autoantigens were identified by both array screening platforms, including a kinase involved in cell adhesion and migration, proteins associated with endocytic and exocytic machinery, a component of the COP9 signalosome complex, a transcriptional repressor and an inhibitory subunit of a nuclear protein phosphatase. Preliminary validation data of these antigens will be presented. Over-represented pathways associated with late stage ovarian cancer were the VEGF signalling pathway and the EGFR1 signalling pathway.
Conclusions: Protein array platforms can be used to identify autoantibody profiles in OC sera. Autoantibodies to p53 were confirmed in 25% of late stage OC patients in line with published data. Pathway analysis performed on antigens identified by autoantibody screening indicated that classical cancer pathways may be deregulated. This indicates that autoantibody profiles detect malignancy associated protein pathway deregulation.
The authors gratefully acknowledge grant support from the Emer Casey Foundation and the clinical contributions of Noreen Gleeson, Tom D'Arcy, Alex Laios, Katherine Astbury and Eamonn McGuinness.
Category: Special Category - Pan-genomic/Pan-proteomic approaches to Cancer
Tuesday, March 20, 2012 9:30 AM
Poster Session III # 276, Tuesday Morning