Clinical relevance of circulating nucleosomes in cancer.
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.
Holdenrieder
Stefan
S
Institute of Clinical Chemistry, University Hospital of Munich, Munich, Germany. Stefan.Holdenrieder@med.uni-muenchen.de
Nagel
Dorothea
D
Schalhorn
Andreas
A
Heinemann
Volker
V
Wilkowski
Ralf
R
von Pawel
Joachim
J
Raith
Hannelore
H
Feldmann
Knut
K
Kremer
Andreas E
AE
Müller
Susanne
S
Geiger
Sandra
S
Hamann
Gerhard F
GF
Seidel
Dietrich
D
Stieber
Petra
P
D014408:Biomarkers, Tumor / Q000097:blood; D003937:Diagnosis, Differential; D006801:Humans; D046911:Macromolecular Substances / Q000097:blood*; D009369:Neoplasms / Q000097:blood* / Q000235:genetics / Q000473:pathology / Q000628:therapy; D009707:Nucleosomes / Q000737:chemistry / Q000378:metabolism*; D011379:Prognosis
D014408:Biomarkers, Tumor; D046911:Macromolecular Substances; D009707:Nucleosomes