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Research ArticleClinical Studies

Novel Serum Nucleosomics Biomarkers for the Detection of Colorectal Cancer

STEFAN HOLDENRIEDER, YOGANIRANJANA DHARUMAN, JENS STANDOP, NICOLAI TRIMPOP, MARIELLE HERZOG, KARINA HETTWER, KIRSTEN SIMON, STEFFEN UHLIG and JAKE MICALLEF
Anticancer Research May 2014, 34 (5) 2357-2362;
STEFAN HOLDENRIEDER
1Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, Bonn, Germany
5Joint Research and Services Center for Biomarker Evaluation in Oncology, Germany
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  • For correspondence: Stefan.Holdenrieder@uni-bonn.de
YOGANIRANJANA DHARUMAN
1Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, Bonn, Germany
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JENS STANDOP
2Department of Surgery, University Hospital Bonn, Bonn, Germany
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NICOLAI TRIMPOP
1Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, Bonn, Germany
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MARIELLE HERZOG
3Belgian Volition SA, Namur, Belgium
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KARINA HETTWER
4QuoData Statistics, Dresden, Germany
5Joint Research and Services Center for Biomarker Evaluation in Oncology, Germany
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KIRSTEN SIMON
4QuoData Statistics, Dresden, Germany
5Joint Research and Services Center for Biomarker Evaluation in Oncology, Germany
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STEFFEN UHLIG
4QuoData Statistics, Dresden, Germany
5Joint Research and Services Center for Biomarker Evaluation in Oncology, Germany
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JAKE MICALLEF
3Belgian Volition SA, Namur, Belgium
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Abstract

Background: To improve prognosis of patients with colorectal cancer, powerful blood-based biomarkers enabling for early detection are needed. As genome-wide DNA hypomethylation is associated with carcinogenesis, and cell-free DNA, thought to be of tumor origin, is found in the circulation of patients with cancer, we investigated the relevance of 5-methylcytosine-modified DNA present in cell-free circulating nucleosomes as a serum biomarker using a convenient enzyme-linked immunosorbent assay (ELISA) technique. Materials and Methods: Serum samples from 90 individuals [24 with colorectal cancer (CRC), 10 with benign colorectal diseases (BCD) and 56 healthy controls (HC)] were tested for the differential diagnostic performance of a novel ELISA for nucleosome-bound methylated DNA. Methodical features, including intra- and interassay imprecision, were tested using serum pools. To minimize interassay variability, values were transformed to adjusted optical densities and robust statistics were applied for clinical evaluation. Findings were later re-evaluated on a set of 113 patients (49 CRC, 26 BCD and 38 HC). Results: Intra- and interassay reproducibility were 3.4% and 15.3%, respectively. Levels of circulating methylated DNA were significantly decreased in CRC and BCD when compared to HC (p<0.05), although there was no difference between BCD and CRC. For discrimination of CRC from HC, the area under the curve in receiver operating characteristic curve was 0.78 and sensitivities were 33% at 95% specificity and 75% at 70% specificity, respectively. The findings were generally confirmed when validated in the second set of patients. Conclusion: Reduced methylation of DNA on circulating nucleosomes detected by ELISA can potentially serve as a diagnostic tool in patients with CRC.

  • Colorectal cancer
  • nucleosomics
  • DNA methylation
  • serum
  • diagnosis
  • Received January 23, 2014.
  • Revision received March 22, 2014.
  • Accepted March 24, 2014.
  • Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved
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Anticancer Research: 34 (5)
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May 2014
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Novel Serum Nucleosomics Biomarkers for the Detection of Colorectal Cancer
STEFAN HOLDENRIEDER, YOGANIRANJANA DHARUMAN, JENS STANDOP, NICOLAI TRIMPOP, MARIELLE HERZOG, KARINA HETTWER, KIRSTEN SIMON, STEFFEN UHLIG, JAKE MICALLEF
Anticancer Research May 2014, 34 (5) 2357-2362;

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Novel Serum Nucleosomics Biomarkers for the Detection of Colorectal Cancer
STEFAN HOLDENRIEDER, YOGANIRANJANA DHARUMAN, JENS STANDOP, NICOLAI TRIMPOP, MARIELLE HERZOG, KARINA HETTWER, KIRSTEN SIMON, STEFFEN UHLIG, JAKE MICALLEF
Anticancer Research May 2014, 34 (5) 2357-2362;
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Keywords

  • colorectal cancer
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