Circulating nucleosomes as epigenetic biomarkers in XXXX .

@entity1 @entity788 @entity5 @entity660 @entity1735
BACKGROUND: To improve the prognosis of @entity1 with @entity788 , new biomarkers are required for earlier, pre-symptomatic diagnosis. Epigenetic mutations take place at the earliest stages of tumorigenesis and therefore offer new approaches for detecting and diagnosing disease. Nucleosomes are the repeating subunits of DNA and histone proteins that constitute @entity1 chromatin. Because of their release into the circulation, intact nucleosome levels in serum or plasma can serve as diagnostic disease biomarkers, and elevated levels have been reported in various @entity5 . However, quantifying nucleosomes in the circulation for @entity5 detection has been challenging due to nonspecific elevation in sera of @entity1 with benign diseases. Here, we report for the first time differential, disease-associated epigenetic profiles of intact cell-free nucleosomes (cfnucleosomes) containing specific DNA and histone modifications as well as histone variants circulating in the blood. The study comprised serum samples from 59 individuals, including 25 @entity1 with resectable @entity788 , 10 @entity1 with benign @entity660 , and 24 healthy individuals using Nucleosomics(  ), a novel ELISA method. RESULTS: Multivariate analysis defined a panel of five serum cfnucleosome biomarkers that gave an area under the curve (AUC) of 0.95 for the discrimination of @entity788 from healthy controls, which was superior to the diagnostic performance of the common @entity788 biomarker, @entity1735 antigen 19-9 (CA 19-9) with an AUC of 0.87. Combining CA 19-9 with a panel of four cfnucleosome biomarkers gave an AUC of 0.98 with an overall sensitivity of 92  % at 90  % specificity. CONCLUSIONS: The present study suggests that global epigenetic profiling of cfnucleosomes in serum using a simple NuQ(  ) immunoassay-based approach can provide novel diagnostic biomarkers in @entity788 .
