Circulating Cell-Free Nucleic Acids: Main Characteristics and Clinical Application

Abstract

Liquid biopsy recently became a very promising diagnostic method that has several advantages over conventional invasive methods. Liquid biopsy may serve as a source of several important biomarkers including cell-free nucleic acids (cf-NAs). Cf-DNA is widely used in prenatal testing in order to characterize fetal genetic disorders. Analysis of cf-DNA may provide information about the mutation profile of tumor cells, while cell-free non-coding RNAs are promising biomarker candidates in the diagnosis and prognosis of cancer. Many of these markers have the potential to help clinicians in therapy selection and in the follow-up of patients. Thus, cf-NA-based diagnostics represent a new path in personalized medicine. Although several reviews are available in the field, most of them focus on a limited number of cf-NA types. In this review, we give an overview about all known cf-NAs including cf-DNA, cf-mtDNA and cell-free non-coding RNA (miRNA, lncRNA, circRNA, piRNA, YRNA, and vtRNA) by discussing their biogenesis, biological function and potential as biomarker candidates in liquid biopsy. We also outline possible future directions in the field.

The Cell-Free Expression of MiR200 Family Members Correlates with Estrogen Sensitivity in Human Epithelial Ovarian Cells

“…Cell-free miRNAs represent a highly promising but understudied area of miRNA biology which might open new avenues in cancer research. Accumulating evidence suggests that cell-free miRNA expression correlates with the occurrence of several malignancies, and thus they are considered to be promising biomarker candidates in liquid biopsy [ 21 , 80 ]. However, less research is available on their biological significance or their application as biomarkers in cell cultures.…”

Comparative Analysis of Cell-Free miR-205-5p, let-7f-5p, and miR-483-5p Expression in Ovarian Cell Cultures and Plasma Samples of Patients with Ovarian Cancer

“…Liquid biopsy is a promising non-invasive diagnostic approach that is based on the quantification of biomarkers in body fluids and has several advantages over conventional tissue biopsies [1,2]. Cell-free counterparts of nucleic acids are considered to be applicable biomarker candidates for liquid biopsy.…”

“…Cell-free counterparts of nucleic acids are considered to be applicable biomarker candidates for liquid biopsy. These include different types of cell-free DNA (e.g., genomic DNA or mitochondrial DNA fragments) and non-coding RNA molecules (e.g., microRNAs, circular RNAs, long non-coding RNAs) [1]. Among non-coding RNA molecules, most studies focus on miRNAs due to the following reasons: (i) they are stable; (ii) easily detectable by molecular biological methods (e.g., qPCR); and (iii) their expression showed good association with the occurrence of several diseases, including cancer.…”

“…Among non-coding RNA molecules, most studies focus on miRNAs due to the following reasons: (i) they are stable; (ii) easily detectable by molecular biological methods (e.g., qPCR); and (iii) their expression showed good association with the occurrence of several diseases, including cancer. This latter is due to the fact that miRNAs affect the expression of several genes involved in cancer progression and invasion; thus, miRNAs might function as oncomirs or tumor suppressors [1][2][3][4].…”

Circulating miRNAs as Tumor Biomarkers: A Preface to the Special Issue

“…Circulating free RNAs (cfRNAs), either as a free molecule alone or in complexes with proteins and lipids, are present in various types of body fluids, such as blood, serum, and plasma [ 1 ]. There are several types of cfRNAs that could be distinguished based on their length and function: microRNA (miRNA), PIWI-interacting RNA (piRNA), tRNA-derived RNA fragments (tRFs), circular RNA (circRNA), long non-coding RNA (lncRNA), and messenger RNA (mRNA) [ 2 ].…”