Circulating exosomes may provide a more sensitive platform to monitor disease progression compared to circulating tumor cells.

Abstract

10580 Background: Circulating tumor cells (CTCs) have been used to monitor disease progression in patients with different types of metastatic cancer. However only 50% of metastatic breast, 57% of metastatic prostate, and 18% of metastatic colon cancer blood specimens have adequate levels of CTCs for clinical laboratory analysis. Levels of exosomes have recently been shown to correlate with tumor progression. Methods: Exosomes from 1 ml of plasma were isolated by ultracentrifugation. CD-81 antibodies were used to capture and measure the exosome level of breast cancer samples (n=14) and healthy controls (n=4). CTCs were measured for all samples using the Cell Search CTC test protocol. Subsequently, EpCam positive exosomes were captured from metastatic breast (n=10), prostate (n=2), and colon cancer (n=3) samples, and compared to healthy controls (n=7). RNA was extracted from these EpCam positive exosomes and microRNA-21 (miR-21) expression was quantified by a qRT-PCR. Results: The preliminary study of breast cancer samples established 11 of the 14 samples (78.6%) had CD-81 specific exosome levels significantly above the level found in the 4 healthy samples (p=0.002). Only 7 of the 14 (50%) specimens analyzed had more than 5 CTCs, the clinical threshold for metastatic breast cancer. Three cancer samples had CD-81 measured exosome levels below the average of normal samples, one of these had >5 CTCs. miR- 21 analysis of 15 additional metastatic cancer specimens, 5 of which had >5 CTCs, found miR-21 averaged 4.2 × 106, 4.82 × 106 and 5.05 × 106 copies in the breast, prostate, and colon cancer samples respectively. Conversely, the plasma specimens from healthy donors collected in EDTA tubes averaged 1.8 × 104 copies of miR21. Conclusions: This study suggests that exosome analysis from plasma samples may offer a greater opportunity to monitor and track disease than CTC analysis, while acknowledging that further study will be necessary to establish clinical definitions of exosome load. Furthermore, tumor-derived exosomes provide the ability to characterize tumor of origin miR content, which demonstrates additional opportunities for tumor-specific exosome-based biomarker analysis from a blood sample. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Caris MPI