Nucleosomes, complexes of
DNA and
histone proteins, are released during cell death into the blood circulation. Elevated serum and plasma levels have been found in various forms of
cancer, but also in
autoimmune diseases and acute situations such as
stroke,
trauma, and during
sepsis. Here, the clinical relevance of circulating
nucleosomes for diagnosis, staging, prognosis, and therapeutic monitoring of
cancer is reviewed. Several studies have shown that levels of
nucleosomes are significantly higher in serum and plasma of
cancer patients in comparison to healthy controls. However, because of elevations of
nucleosome levels in patients with benign diseases relevant for differential diagnosis, they are not suitable for
cancer diagnosis. Concerning
tumor staging,
nucleosome levels correlate with
tumor stage and presence of
metastases in
gastrointestinal cancer, but not in other
tumor types. Prognostic value of circulating
nucleosomes is found in
lung cancer in univariate analyses, but not in multivariate analyses. Circulating
nucleosomes are most informative for the monitoring of cytotoxic
therapy. Strongly decreasing levels are mainly found in patients with remission of disease, whereas constantly high or increasing values are associated with progressive disease during chemo- and
radiotherapy. In addition,
therapy outcome is already indicated by the nucleosomal course during the first week of chemo- and
radiotherapy in patients with lung, pancreatic, and
colorectal cancer as well as in
hematologic malignancies. Despite their non-
tumor-specificity, kinetics of
nucleosomes are valuable markers for the early estimation of therapeutic efficacy and may be helpful to adapting early
cancer therapy in the future.