Evaluation of exosomal non-coding RNAs in cancer using high-throughput sequencing

Abstract

Clinical oncologists need more reliable and non-invasive diagnostic and prognostic biomarkers to follow-up cancer patients. However, the existing biomarkers are often invasive and costly, emphasizing the need for the development of biomarkers to provide convenient and precise detection. Extracellular vesicles especially exosomes have recently been the focus of translational research to develop non-invasive and reliable biomarkers for several diseases such as cancers, suggesting as a valuable source of tumor markers. Exosomes are nano-sized extracellular vesicles secreted by various living cells that can be found in all body fluids including serum, urine, saliva, cerebrospinal fluid, and ascites. Different molecular and genetic contents of their origin such as nucleic acids, proteins, lipids, and glycans in a stable form make exosomes a promising approach for various cancers' diagnoses, prediction, and follow-up in a minimally invasive manner. Since exosomes are used by cancer cells for intercellular communication, they play a critical role in the disease process, highlighting the importance of their use as clinically relevant biomarkers. However, regardless of the advantages that exosome-based diagnostics have, they suffer from problems regarding their isolation, detection, and characterization of their contents. This study reviews the history and biogenesis of exosomes and discusses non-coding RNAs (ncRNAs) and their potential as tumor markers in different types of cancer, with a focus on next generation sequencing (NGS) as a detection method. Moreover, the advantages and challenges associated with exosome-based diagnostics are also presented.

Keywords: Biomarkers; Cancer; Exosome; NGS; Nucleic acids; ncRNAs.

Fig. 1

Biogenesis mechanism of exosomes, which starts with the development of the endosome and then forms multivesicular bodies (MVBs). MVBs can both integrate with lysosomes for degradation or fuse with the cellular membrane to release exosomes. These processes can happen by both ESCRT-dependent and ESCRT-independent pathways

Fig. 2

Process of exosomal biomarker identification using NGS. NA: nucleic acid; NGS; next generation sequencing