Extracellular vesicle molecular signatures characterize metastatic dynamicity in ovarian cancer

Gonda, A.; Zhao, N.; Shah, J. V.; Siebert, J. N.; Gunda, S.; Inan, B.; Kwon, M.; Libutti, S. K.; Moghe, P. V.; Francis, N. L.; Ganapathy, V.

doi:10.1101/2021.04.22.440951

bioRxiv · 10.1101/2021.04.22.440951

Extracellular vesicle molecular signatures characterize metastatic dynamicity in ovarian cancer

Gonda, A.·Zhao, N.·Shah, J. V.·Siebert, J. N.·Gunda, S.·Inan, B.·Kwon, M.·Libutti, S. K.·Moghe, P. V.·Francis, N. L.·Ganapathy, V.

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Abstract

Late-stage diagnosis of ovarian cancer drastically lowers 5-year survival rate from 90% to 30%. Early screening tools that use non-invasive sampling methods combined with high specificity and sensitivity can significantly increase survival. Emerging research employing blood-based screening tools have shown promise in non-invasive detection of cancer. Our findings in this study show the potential of a small extracellular vesicle (sEV)-derived signature as a non-invasive longitudinal screening tool in ovarian cancer. We identified a 7-gene panel in these sEVs that overlapped with an established tissue-derived metastatic ovarian carcinoma signature. We found the 7-gene panel to be differentially expressed with tumor development and metastatic spread. While there were quantifiable changes in genes from the 7-gene panel in plasma-derived sEVs from ovarian cancer patients, we were unable to establish a definitive signature due to low sample number. The most notable finding was a significant change in the ascites-derived sEV gene signature that overlapped with that of the plasma-derived sEV signature at varying stages of disease progression. Taken together our findings show that differential expression of metastatic genes derived from circulating sEVs present a minimally invasive screening tool for ovarian cancer detection and longitudinal monitoring of molecular changes associated with progression and metastatic spread.

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Gonda, A., Zhao, N., Shah, J. V., Siebert, J. N., Gunda, S., Inan, B., Kwon, M., Libutti, S. K., Moghe, P. V., Francis, N. L., Ganapathy, V.. 2021-04-22. Extracellular vesicle molecular signatures characterize metastatic dynamicity in ovarian cancer. https://doi.org/10.1101/2021.04.22.440951

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