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Title: Circulating autoantibodies as biomarkers of early stage, high grade serous ovarian cancer.
Authors: Stephens, Andrew
Jobling, Thomas
Other Authors: Wilson, Amy
Moffitt, Laura
Duffield, Nadine
Plebanski, Magdalena
Keywords: Ovarian Cancer
High Grade Serous Epithelial Ovarian Cancers
Early Diagnosis
Tumor Antigens
Clinical Manifestation
Benign Cystadenoma
Benign Cystadenofibroma
High-Content Protein Arrays
Functional Enrichment Analysis
Ingenuity Pathways Analysis
Gene Ontology
Enzyme-Linked Immunosorbent Assays
Cell Cycle
Cell-Cell Signalling
Inflammatory Response
Receiver-Operator Curve Analysis
Cancer Services Clinical Institute, Epworth HealthCare, Victoria, Australia
Epworth Research Institute, Epworth HealthCare, Victoria, Australia
Issue Date: Jun-2017
Citation: Epworth Research Institute Research Week 2017; Poster 59: pp 83
Conference Name: Epworth Research Institute Research Week 2017
Conference Location: Epworth Research Institute, Victoria, Australia
Abstract: INTRODUCTION: High grade serous epithelial ovarian cancers (HGSOCs) are typically diagnosed at an advanced stage, and account for ~90% of all ovarian cancer related deaths. Early diagnosis, prior to extra-ovarian spread, is associated with improved survival. There remains an unmet clinical need to identify novel biomarkers for the early-stage diagnosis of HGSOCs. Anti-tumor immune responses can generate auto-antibodies (AAbs) against tumor antigens well before the clinical manifestation of disease. We have performed a pilot study to identify AAbs as potential biomarkers for the detection of early-stage HGSOC. METHODS: Plasma samples were collected from chemo-naïve, previously untreated patients representing early (FIGO stage I) or advanced (FIGO stage III) HGSOC; and from patients with benign cystadenoma, benign cystadenofibroma or no diseases (n=20/group) and no prior history of malignancy. Samples were randomly assigned to either "discovery" or "validation" cohorts (n=10/group) and the presence and reactivity of AAbs (IgG, IgA, and IgM) determined using high-content protein arrays. Functional enrichment analyses were performed using Ingenuity Pathways Analysis and Gene Ontology. Enzyme-linked immunosorbent assays (ELISA) were developed against selected antigens, and their prevalence in each cohort assessed. RESULTS: In total 567 antigens were significantly associated with malignancy, and were functionally enriched for processes including cell cycle, growth and proliferation (early stage); and cell-cell signaling and inflammatory response (late-stage). Increased reactivity of two antigens - CCDC115 and HSF1 - was independently validated by ELISA in early stage patients, in both discovery and validation cohorts. Receiver-operator curve analysis at 90% sensitivity gave specificities of 88.9% (likelihood ratio 8.4, AUC 0.88) and 90% (likelihood ratio 4.5, AUC 0.96) respectively, for the detection of early-stage disease. CONCLUSIONS: Circulating auto-antibodies against CCDC115 and HSF1 represent potential biomarkers of early-stage HGSOC. This pilot study has established the workflow for expanded investigations to identify clinically relevant AAbs as markers of ovarian cancer.
Type: Conference Poster
Affiliated Organisations: Centre for Cancer Research, Hudson Institute of Medical Research, Victoria, Australia
Department of Immunology and Pathology, Monash University, Victoria, Australia
Department of Obstetrics and Gynaecology, Monash Medical Centre, Victoria, Australia
Department of Molecular and Translational Sciences, Monash University, Victoria, Australia
Type of Clinical Study or Trial: Randomized Clinical Trial
Appears in Collections:Cancer Services
Research Week

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