Liquid biopsy in ovarian cancer: recent advances in circulating extracellular vesicle detection for early diagnosis and monitoring progression

Lei Chang, Jie Ni, Ying Zhu, Bairen Pang, Peter Graham, Hao Zhang, Yong Li, Lei Chang, Jie Ni, Ying Zhu, Bairen Pang, Peter Graham, Hao Zhang, Yong Li

Abstract

The current biomarkers available in the clinic are not enough for early diagnosis or for monitoring disease progression of ovarian cancer. Liquid biopsy is a minimally invasive test and has the advantage of early diagnosis and real-time monitoring of treatment response. Although significant progress has been made in the usage of circulating tumor cells and cell-free DNA for ovarian cancer diagnosis, their potential for early detection or monitoring progression remains elusive. Extracellular vesicles (EVs) are a heterogeneous group of lipid membranous particles released from almost all cell types. EVs contain proteins, mRNA, DNA fragments, non-coding RNAs, and lipids and play a critical role in intercellular communication. Emerging evidence suggests that EVs have crucial roles in cancer development and metastasis, thus holding promise for liquid biopsy-based biomarker discovery for ovarian cancer diagnosis. In this review, we discuss the advantages of EV-based liquid biopsy, summarize the protein biomarkers identified from EVs in ovarian cancer, and highlight the utility of new technologies recently developed for EV detection with an emphasis on their use for diagnosing ovarian cancer, monitoring cancer progression, and developing personalized medicine.

Keywords: Extracellular vesicle; diagnosis; liquid biopsy; ovarian cancer.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

Figures

Figure 1
Figure 1
Profiling of OC patient exosomes with nPLEX. (A) An image showing an nPLEX chip integrated with a multichannel microfluidic cell for independent and parallel analyses. (B) Analysis of ascites-derived exosomes from OC and healthy patients by the nPLEX sensor. (C) Exosomal protein levels of EpCAM and CD24 in ascites samples from patients measured by nPLEX. (D) Longitudinal monitoring of treatment responses in ascites samples from OC patients before and after chemotherapy with nPLEX. Reprinted by permission from Springer Nature: BMC Springer Nature, Nature Biotechnology. Label-free detection and molecular profiling of exosomes with a nano-plasmonic sensor, H. Im et al., copyright 2014.
Figure 2
Figure 2
iMEX for clinical applications. (A) iMEX assay for clinical OC plasma analysis with CD63, EpCAM, CD24, and CA125 markers. (B) EpCAM and CD24 levels analyzed by the iMEX assay were much higher in OC patients. (C) Longitudinal monitoring of drug treatment responses with the iMEX assay. EpCAM and CD24 levels in responders were decreased significantly, but their levels in nonresponders were stable (EpCAM) or increased (CD24) after treatment. Reprinted with permission from S. Jeong et al., Integrated Magneto-Electrochemical Sensor for Exosome Analysis, ACS Nano, 10 (2016) 1802-1809. Copyright (2016) American Chemical Society.

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