Liquid biopsy: Exosomal microRNAs as novel diagnostic and prognostic biomarkers in cancer

Abstract

Background: Detecting cancer at an early stage before clinical manifestation could be an effective strategy to decrease cancer mortality. Thus, identifying liquid biopsy biomarkers with high efficacy could be a promising approach for non-invasive diagnosis of cancer.

Main text: Liquid biopsies are increasingly used as a supplement to biopsy, as it enables disease progression to be detected months before clinical and radiographic confirmation. Many bodily fluids contain exosomal microRNAs (miRNAs) which could provide a new class of biomarkers for early and minimally invasive cancer diagnosis due to the stability of miRNAs in exosomes. In this review, we mainly focused on the exosomal miRNAs (liquid biopsy) as biomarkers in the diagnosis and prognosis of various cancers.

Conclusion: Exosomal miRNAs can be used as diagnostic and prognosis biomarkers that provide unique insights and a more dynamic perspective of the progression and therapeutic responses in various malignancies. Therefore, the development of novel and more sensitive technologies that exploit exosomal miRNAs should be a priority for cancer management.

Keywords: Biomarkers; Cancer; Exosomal miRNAs; Liquid biopsy; Non-invasive diagnosis.

Fig. 1

Representing the overview of liquid biopsy

Fig. 2

Representing the biogenesis of Exosomes. Exosomes are produced by intraluminal vesicles (ILVs). The cargoes like nucleic acids, lipids and proteins are absorbed by the cells and are carried to early endosomes via the endocytotic pathway. Multivesicular bodies (MVBs) are formed by the maturation of early endosomes. Nucleic acids like miRNAs, DNAs, and RNAs, proteins like cytoplasmic proteins, tetraspanins, and membrane receptors, and lipids like ceramides and cholesterol are all integrated into exosomes during the ILV production process. Finally, exosomes are released into the extracellular space when MVBs fuse with cellular membranes

Fig. 3

Representing sorting mechanism of miRNAs into exosomes. miRNA genes are transcribed by RNA polymerase II into primary miRNAs (pri-miRNAs), which are then processed by Drosha complex into precursor miRNAs (pre-miRNAs), which are then exported into cytoplasm by the exportin 5 complex. Pre-miRNAs are then processed by the Dicer complex into mature miRNAs, which are further sorted into exosomes through four potential pathways namely: a nSMase2- dependent pathway; b 3′ end miRNA sequence-dependent pathway; c Sumoylated hnRNPs- dependent pathway; d miRISC related pathway. Exosomal miRNAs perform a functional role after being transported into recipient cells