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Session 8, Abstract 50

DETERMINING THE SUBCLINICAL SIGNIFICANCE OF CIRCULATING TUMOR CELLS IN EPITHELIAL OVARIAN CANCER THROUGH GENOMIC AND PROTEOMIC PROFILING

Serena Zheng* (Peter Kuhn), University of Southern California, Bridge Institute, 3430 S. Vermont Ave., Los Angeles, CA 90089-3303.

Epithelial ovarian cancer (EOC) is a leading cause of cancer death in women. While chemotherapy is initially largely effective, an 80% chance of relapse, often accompanied by acquired resistance, remains. These characteristics likely contribute to the poor prognoses so closely associated with the disease, and predicting relapse remains a challenge. Analysis of circulating tumor cells (CTCs) found in EOC patient blood samples collected post-chemo may provide insight into the genomic and proteomic abnormalities of the disease, but the utility of CTCs as subclinical indicators of relapse has yet to be determined. Peripheral blood samples collected post-chemo from 18 EOC patients (papillary serous, stages II-IV) were evaluated using the High Definition Single Cell Analysis (HDSCA) Assay for DNA copy number variation (CNV) and proteomic profiling. CTCs were detected (≥5 CTCs/mL) in 5 (28%) of these patients, 2 of whom relapsed. Single cell CTC CNV profiles from one of these recurrent patients showed cyclin E1 amplification on chromosome 19 and ARID1A gene deletion on chromosome 1, genomic alterations consistent with EOC. In proteomics, imaging mass cytometry revealed these CTCs were negative for epithelial markers but positive for mesenchymal ones, suggesting that the CTCs found in this patient who relapsed were likely undergoing epithelial-mesenchymal transition—where epithelial cells gain invasive capabilities associated with metastasis. Preliminary data obtained for CTCs found in non-recurrent patients showed fewer genomic aberrations, but further genomics and proteomic analysis is needed. Earlier detection of relapse, and subsequent personalized treatment, could eventually lead to more favorable prognoses in EOC patients.