Extracellular Vesicle-DNA: The Next Liquid Biopsy Biomarker for Early Cancer Diagnosis?

Abstract

After a short introduction about the history of liquid biopsy, aimed to noninvasively replace the common tissue biopsy as a help for cancer diagnosis, this review is focused on extracellular vesicles (EVs), as the main third component, which is now coming into the light of liquid biopsy. Cell-derived EV release is a recently discovered general cellular property, and EVs harbor many cellular components reflecting their cell of origin. This is also the case for tumoral cells, and their cargoes might therefore be a "treasure chest" for cancer biomarkers. This has been extensively explored for a decade, but the EV-DNA content escaped this worldwide query until recently. The aim of this review is to gather the pilot studies focused on the DNA content of circulating cell-derived EVs, and the following five years of studies about the circulating tumor EV-DNA. The recent preclinical studies about the circulating tEV-derived gDNA as a potential cancer biomarker developed into a puzzling controversy about the presence of DNA into exosomes, coupled with an increased unexpected non vesicular complexity of the extracellular environment. This is discussed in the present review, together with the challenges that need to be solved before any efficient clinical transfer of EV-DNA as a quite promising cancer diagnosis biomarker.

Tumor biomarkers for diagnosis, prognosis and targeted therapy

“… 115 Currently, liquid biopsy is used to detect cfDNA, cell-free RNA, CTCs, extracellular vesicles, 116 , 117 ctDNA, 118 circulating RNA, and exosomes 119 , 120 in blood or other body fluids. 116 , 121 Liquid biopsy can enhance patient overall survival (OS) by improving early cancer detection and monitoring treatment response continuously. Thus, liquid biopsies are widely used in the clinical biomarker screening of tumors, such as endometrial cancer, 122 lung cancer, 123 pancreatic cancer, 124 CRC, 125 melanoma, 126 renal cell carcinoma (RCC), 127 breast cancer, ovarian cancer, cervical cancer, and bladder cancer.…”

DNA Content in Embryonic Extracellular Vesicles Is Independent of the Apoptotic Rate in Bovine Embryos Produced In Vitro

“…Therefore, EVs have been proposed as disease biomarkers [18,19]. The use of released and circulating EVs for molecular diagnosis excludes the need for cellular biopsy, and is a less invasive method, often providing a more representative sample of a tissue or organ function [20].…”