Proteomic biomarker for detection of ovarian cancer using gynecologic liquid biopsy

Abstract The vast majority of high-grade ovarian cancer (HGOC) patients are diagnosed at a metastatic stage, resulting in exceptionally low cure rates. Current screening options fail to improve mortality due to the absence of early-stage-specific biomarkers and the poor systemic representation of early-stage tumors. We postulated that a gynecologic liquid biopsy, such as utero-tubal lavage (UtL), may identify localized lesions better than systemic approaches of serum/plasma analysis. Furthermore, while mutation-based assays are challenged by the rarity of tumor DNA within nonmutated DNA, analyzing the proteomic profile may potentially enable earlier detection, as it reveals perturbations in both the tumor compartment as well as in its microenvironment. To attain deep proteomic coverage and overcome the high dynamic range of this body fluid, we isolated microvesicles and performed mass spectrometric proteomic analysis of the UtL samples. Liquid biopsies from HGOC patients (n=85), controls (n=183), and healthy BRCA mutation carriers (n=37), were divided into discovery and validation sets. Data-dependent analysis of the samples on the Q-Exactive mass spectrometer provided depth of 8,578 UtL proteins in total, and on average ~3,000 proteins per sample. We used support vector machine algorithms for sample classification, and crossed three feature-selection algorithms, to construct and validate a 9-protein classifier with 63% sensitivity and 73% specificity. The signature correctly identified all Stage I lesions and highlighted increased risk in healthy BRCA carriers. These results demonstrate the potential power of microvesicle-based proteomic biomarkers for early cancer diagnosis but require integration with other biomarker types for improved prediction. Citation Format: Georgina D. Barnabas, Keren Bahar-Shany, Stav Sapoznik, Jacob Korach, Tamar Perri, Eitan Friedman, David Stockheim, Ariella Jakobson-Setton, Ram Eitan, Limor Helpman, Yfat Kadan, Sarit Aviel-Ronen, Michal Harel, Tamar Geiger, Keren Levanon. Proteomic biomarker for detection of ovarian cancer using gynecologic liquid biopsy [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr B06.