Circulating free DNA are degraded DNA fragments released to the blood plasma. cfDNA can be used to describe various forms of DNA freely circulating the bloodstream, including circulating tumor DNA  and cell-free fetal DNA (cffDNA). Elevated levels of cfDNA are observed in cancer, especially in advanced disease. There is evidence that cfDNA becomes increasingly frequent in circulation with the onset of age. cfDNA has been shown to be a useful biomarker for a multitude of ailments other than cancer and fetal medicine. This includes but is not limited to trauma, sepsis, aseptic inflammation, myocardial infarction, stroke, transplantation, diabetes, and sickle cell disease. cfDNA is mostly a double-stranded extracellular molecule of DNA, consisting of small fragments (70 to 200 bp)  and larger fragments (21 kb)  and has been recognized as an accurate marker for the diagnosis of prostate cancer and breast cancer.

Other publications confirm the origin of cfDNA from carcinomas and cfDNA occurs in patients with advanced cancer. Cell‐free DNA (cfDNA) is present in the circulating plasma and in other body fluids.

Liquid biopsy, a term relative to tissue biopsy, is a technical way to analyze the nonsolid biological tissue by detection of cells and free DNA that enter body fluids. Liquid biopsy refers to the real-time monitoring of the dynamic alterations of disease by detecting circulating tumor cells (CTCs), circulating cell-free DNA (cfDNA), exosomes and so on. This technique has great application value as a tool for disease early diagnosis, real-time progression monitoring, curative effect observation and evaluation, prognosis assessment, and metastasis risk analysis, with the added benefit of being noninvasive and flexible for repeat tumor sampling.

The concentration, integrity, genetic, and epigenetic alternations in the cfDNA may suggest pathological conditions of the body, such as inflammation, autoimmune diseases, stress, or even malignancies. Different disease-associated molecular characteristics can be detected as the indicators of pathological conditions in the plasma of patients, including the total level and fragment, copy-number aberrations, methylation changes, single-nucleotide mutations cancer-derived viral sequences, and chromosomal rearrangements. cfDNA from patients with malignancies (cell-free tumor DNA, ctDNA) contains variants as those in the tumor tissue cells, thus allowing noninvasive assessment of tumor in real time. ctDNA is a very promising tumor biomarker for cancer diagnosis and monitoring, prognosis assessment, and personalized medication guidance compared with conventional serum markers.

The size of cfDNA

The length of cfDNA from patients differs from that of healthy groups, which may suggest some kinds of physiological or pathological conditions, including pregnancy, cancer, liver/bone marrow transplantation, SLE, and many other clinical scenarios such as stroke, autoimmune disorders, and myocardial infarction. cfDNA has been used as an independent marker for prenatal screening and also has great applicable value in the disease prognosis and monitoring, particularly in cancer. The appearance of cfDNA conforms to the current trend of precision medicine in the disease and achieves accurate diagnosis and precise treatment. However, there are many challenges in the real clinic applications.

The study of cfDNA is still in its infancy, and a lot of in-depth research is needed to further confirm its clinical application value.

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