AS734 - Identification and validation of tumor-associated autoantibodies as markers for early detection of ovarian cancer
Investigator Names and Contact Information
Rudolf Kaaks (r.kaaks@dkfz.de)
Renée Turzanski Fortner (r.fortner@dkfz.de)
Introduction/Intent
Current strategies for earlier-stage detection of epithelial ovarian cancer [EOC] use a combination of blood-based biomarkers and trans-vaginal ultrasound. The best available EOC early detection biomarker is CA125; however, diagnostic discrimination for early-stage disease is poor. Additional early detection markers are needed, and we propose to investigate tumor associated auto-antibodies [TAAbs] as such markers.
The major aims of the study are to (i) identify novel, diagnostically useful TAAb markers through a 3-stage discovery and validation study in nested case-control studies, using protein binding arrays and ELISA assays; (ii) cross-validate additional TAAbs identified by other groups; (iii) develop and cross-validate combined TAAb panels alone and together with established marker CA125.
To achieve these aims, we will apply state-of-the-art immunoprofiling technologies to pre-diagnosis serum samples from EOC cases (and cancer-free controls) within the world’s largest prospective cohort studies. ELISA assays will be used for the validation components of the study. A limitation of most discovery studies for OC early detection markers is that biomarkers were first identified and tested in case-control comparisons of advanced cases. This may lead to the discovery of markers that are only predictive for late-stage disease. A unique strength of this study is that we will conduct the discovery stage in samples collected shortly (<15 months) prior to diagnosis. Validation will be carried out in independent case-control sets. 100 μL of serum or plasma for 166 OC cases diagnosed <18 months after blood collection, plus 322 matched controls (2 per case), is requested from the Women’s Health Initiative.
Specific Aims:
The specific aim of this project is to validate a set of candidate tumor associated autoantibodies (AAbs) identified in an immuno-proteomics scans in the Brigham and Women’s Hospital (BWH) bio-repository and the European Prospective Investigation into Cancer and Nutrition (EPIC), alone and in combination with CA125.
