Exosome Gene Signatures Characterize Metastatic Dynamicity.

Abstract Early diagnosis and effective tumor monitoring can significantly alter clinical outcomes of ovarian cancer patients. Innovative tools are needed to enhance the sensitivity and specificity of current monitoring modalities. Extracellular vesicles, or exosomes, have shown to be promising conduits of diagnostic biomarkers to aid in tumor detection as evidenced by Exosome Diagnostics' new ExoDx Prostate (IntelliScore) test that uses exosomal markers to differentiate between benign prostate disease and early cancer (Tutrone, R., Donovan, M.J., Torkler, P. et al. Clinical utility of the exosome based ExoDx Prostate(IntelliScore) EPI test in men presenting for initial Biopsy with a PSA 2-10 ng/mL. Prostate Cancer Prostatic Dis 23, 607-614 (2020)). The potential of these vesicles however goes beyond simple diagnostic power of cancer detection. Due to the onco-specific contents packaged and the minimally invasive, low risk accessibility, exosomes have the capacity to be used as longitudinal monitoring tools to characterize early molecular changes at all stages of the disease. We hypothesized that the dynamicity of ovarian tumors during progression and metastatic development is reflected in exosomes. In order to test this we isolated exosomes and used qPCR to analyze exosomal gene signatures from a mouse model of ovarian cancer. SKOV3 ovarian cancer tumor cells were injected into mice and allowed to grow for 3 weeks. Plasma was collected from mice at 5-7 day increments and exosomes were extracted. Multiple established metastatic genes in ovarian cancer were evaluated and 4 genes, Lox, THBS1, TIMP3, and β-actin, were found to be differentially expressed in correlation with 3 translationally pertinent assessments: presence or absence of tumors, levels of metastatic burden, and longitudinal tumor progression. Gene expression patterns were compared with exosomal gene signatures extracted from human ovarian patient plasma and found to express similar patterns. These results support the diagnostic potential of using exosomal genetic signatures to detect early metastatic development and to facilitate longitudinal tracking of tumor progression. Citation Format: Amber Gonda, Jay V. Shah, Jake N. Siebert, Nanxia Zhao, Mi Jung Kwon, Prabhas V. Moghe, Nicola Francis, Vidya Ganapathy. Exosome gene signatures characterize metastatic dynamicity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2831.