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Oncotarget. 2017 Oct 20;9(12):10247-10258. doi: 10.18632/oncotarget.21908. eCollection 2018 Feb 13.

Circulating cell-free nucleosomes as biomarkers for early detection of colorectal cancer.

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Department of Surgical Gastroenterology 360, Hvidovre Hospital, Hvidovre, Denmark.
Belgian Volition SPRL, Isnes, Belgium.
Institute of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.


The aim was to evaluate serum levels of circulating cell-free nucleosomes (ccfn) containing a variety of epigenetic signals including 5-methylcytosine DNA, histone modifications H3K9Me3, H3K9Ac, H3S10PO4, H3K36Me3, H4K20Me3, H4PanAc and pH2AX, nucleosome variant H2AZ and nucleosome adducts with HMGB1 and EZH2 as well as ccfn per se, in addition to develop and evaluate predictor models based on the above mentioned ccfn and including serum levels of carcinoembryonic antigen (CEA), in early detection of colorectal cancer (CRC). Blood-samples were collected from 4,105 individuals undergoing colonoscopy. Serum levels of ccfn and CEA were determined using enzyme-linked immunosorbent assays platforms. Individual assessment of levels of ccfn showed area under the receiver operating characteristic curve (AUCROC) = 0.525-0.576 in discrimination of individuals with CRC from individuals with non-malignant findings. Predictor models including ccfn containing 5-methylcytosine DNA, CEA, age and gender improved results (AUCROC = 0.736, sensitivity = 0.37 at specificity = 0.90). Further improvement was achieved in discrimination of individuals with CRC from individuals with clean colorectum (AUCROC = 0.840, sensitivity = 0.57 at specificity = 0.90). The levels of ccfn among patients with CRC appeared to be stage-independent. In conclusion, the performance of the developed predictor models is potentially promising in early detection of CRC.


biomarkers; colorectal neoplasms; early detection of cancer; histone code; tumor

Conflict of interest statement

CONFLICTS OF INTEREST Marielle Herzog and Jake Micallef are employed by Belgian Volition SPRL, Isnes, Belgium. The remaining authors have no conflict of interest to declare.

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