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

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.

Extracellular Vesicles as Signaling Mediators and Disease Biomarkers across Biological Barriers

“…At the same time, the EV content displaying dynamic disease-specific information has a high potential even in the development of new prognostic biomarkers. EVs have been already proposed as reliable diagnostic/prognostic biomarkers in many clinical settings, such as coronary artery disease [108], renal [109], liver [110], neurodegenerative [107], and autoimmune [111] diseases, as well as in systemic sclerosis [112], in urological [113], hepatobiliary [103], and hematological [114] malignances, and in breast [115], lung [116], and ovarian cancers [117], and in cancer care [118].…”

EVs as Potential New Therapeutic Tool/Target in Gastrointestinal Cancer and HCC

“…From this perspective, it appears that EVs may be a good candidate as a molecular biomarker of disease activity and treatment monitoring. Several lines of evidence suggest that EVs can potentially be used as non-invasive liquid biopsies for cancer diagnosis [ 31 , 32 , 33 , 34 , 35 ]. Especially utilising the power of artificial intelligence (AI) in differentiating proteomic EV profiles into cancer bearing or non cancer bearing patients and even to reveal the associated tumour entity [ 36 ].…”

Insight updating of the molecular hallmarks in ovarian carcinoma

“…There has been considerable interest in the use of non-invasive liquid biopsies to monitor and diagnose early relapse in patients with OC [ 90 ]. Up to now, although the study of CA-125 and HE4 levels in blood has received FDA approval as predictive biomarkers and for the detection of recurrent disease after the completion of first-line treatment, several studies show their low sensitivity in early stages of the disease [ 91 ].…”