Cell-free Nucleic Acids, Liquid Biopsy and Human Diseases

The discovery of cell-free nucleic acids can be dated back to 1948, when the french scientists Mandel and Metais reported the existence of DNA in the serum. Later, tumor- and fetal-derived cell-free DNA were found in the plasma/serum in 1990s, which leads to an emerging research field known as “liquid biopsy”. In recent years, with the development of next generation sequencing, cell-free DNA has been successfully used in various clinical applications, such as noninvasive prenatal testing and cancer diagnosis. Following such great success, more and more studies explored the fundamental characteristics of cell-free DNA, such as its tissue origin, biogenesis, fragment size, fragment ending patterns, etc. In addition, researchers realized that cell-free DNA widely exists in different body fluids, such as blood, urine, salivary, amniotic fluid and cerebral spinal fluid, which also show strong relationships with various physical and pathologic conditions. Nowadays, the research of cell-free DNA expands to maternal and fetal medicine, cancer, aging, pathogenic diseases, organ transplantation, sport exercises, human evolution, and many more, making cell-free DNA one of the most active research areas with high translational potentials.

In addition to cell-free DNA, various types of cell-free RNA can also be detected in the circulation as the key components of extracellular vesicles (e.g., exosomes and microvesicles), including messenger RNA, microRNA, long non-coding RNA, circular RNA, etc. Current studies of cell-free RNA mainly focus on the early detection and diagnosis of malignances, survival prediction, and recurrence surveillance as valuable cancer biomarkers, while the regulatory roles of these molecules inside extracellular vesicles attract ever growing attentions. This expands the concept of liquid biopsy in cancer diagnosis, in which the circulating tumor cells and circulating cell-free DNA have already been proven to be the excellent tools in exploring the biological mechanisms of cancer metastasis and prognosis monitoring.

In this Research Topic, we aim to present the most updated original research and reviews of the current understanding of blood-based analytes as well as their connections with human diseases. We welcome topics from the following areas:

1. Mechanism of biogenesis and turnover of cell-free nucleic acids from different tissues in normal and pathological conditions
2. New technologies, methods, or algorithms of characterizing molecular features of cell-free nucleic acids
3. Cell-free nucleic acids as the biomarkers of human diseases, and the validation of using cell-free nucleic acids for clinical testing for human diseases
4. Regulatory roles of cell-free nucleic acids to different health conditions or diseases as molecular signals in body fluid
5. Cell-free DNA, cell-free RNA, and circulating tumor cells studies that shed lights on the biology to tumorigenesis and mechanism of cancer metastasis.
6. Other new emerging areas involving cell-free nucleic acids research, such as cross-analysis of cell-free nucleic acids with other `omics' data, big data of cell-free nucleic acids and evolution, etc.