Abstract AP08: DEVELOPMENT OF A MULTI-PROTEIN CLASSIFIER FOR OVARIAN CANCER DETECTION BY SIMULTANEOUS MEASUREMENT OF 92 SERUM PROTEINS ON PROSEEK MULTIPLEX ONCOLOGY II PLATES

Abstract

Abstract There are no FDA approved screening tools for detecting ovarian cancer in the general population. The two best known ovarian cancer biomarkers, CA125 and HE4, are neither adequately sensitive nor specific when used alone to screen the general population for early stage disease. By using a combination of protein biomarkers for screening, it may be possible to increase the sensitivity and specificity over CA125 alone. In this study, we used Proseek Multiplex Oncology II plates to simultaneously measure the expression of 92 cancer-related proteins in serum using proximity extension assays. This technology combines the sensitivity of the polymerase chain reaction with the specificity of antibody-based detection methods, allowing multiplex biomarker detection and high throughput quantification. We analyzed one microliter of serum from 61 women with advanced stage high grade serous ovarian cancer and compared the values obtained to 88 age-matched healthy women. Principle component analysis and unsupervised hierarchical clustering separated the ovarian cancer patients from the healthy, with minimal misclassification. Data from the Proseek plates for CA125 levels exhibited a strong correlation with previously measured clinical values for CA125 (correlation coefficient of 0.91). CA125 and HE4 were detected at low levels in samples from healthy women, while higher levels were observed in the ovarian cancer cases. We identified 52 proteins that differed significantly (p < 0.006) between ovarian cancer and healthy samples; several of which are novel serum biomarkers for ovarian cancer. In total, 40 proteins had an estimated area under the ROC curve of 0.70 or greater. CA125 alone achieved a sensitivity of 93.4% at a specificity of 98%. However, by adding five proteins to CA125, we increased the assay sensitivity to 98.4%, while holding the specificity fixed at 98%. Our data demonstrate that the Proseek technology can replicate the results established by conventional clinical assays for known biomarkers, identify new candidate biomarkers, and improve the sensitivity and specificity of CA125 alone. Citation Format: Amy P.N. Skubitz, Kristin L.M. Boylan, Kate Geschwind, Qing Cao, Timothy K. Starr, Melissa A. Geller, Joseph Celestino, Robert C. Bast Jr., Karen H. Lu, and Joseph S. Koopmeiners. DEVELOPMENT OF A MULTI-PROTEIN CLASSIFIER FOR OVARIAN CANCER DETECTION BY SIMULTANEOUS MEASUREMENT OF 92 SERUM PROTEINS ON PROSEEK MULTIPLEX ONCOLOGY II PLATES [abstract]. In: Proceedings of the 12th Biennial Ovarian Cancer Research Symposium; Sep 13-15, 2018; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2019;25(22 Suppl):Abstract nr AP08.