Novel Serum Biomarkers Detect Colorectal Cancer

There is a critical clinical need for sensitive and specific blood-based biomarkers for better and earlier detection of colorectal cancer (CRC) as well as for therapy stratification and monitoring.

A convenient enzyme-linked immunosorbent assay (ELISA) technique which measures the levels of circulating nucleosomes carrying 5-methycytosine in serum samples of patients with CRC has been tested for differential diagnostic relevance.


Scientists at University Hospital Bonn (Germany) studied 90 serum samples from 24 patients with CRC: 10 with benign colorectal diseases (BCD; mainly diverticulitis, polyps and inflammatory bowel disease) and 56 healthy controls (HC). The cancer group included 10 patients with colonic, 9 with rectal and 5 with sigmoidal cancer; at least 15 had metastatic disease. Findings were later reevaluated on a set of 113 patients including 49 CRC, 26 BCD, and 38 HC. Samples were collected from patients between January 2011 and August 2012 at the time of active disease.

Nucleosome-bound methylated DNA was measured using the NuQ-X ELISA (VolitionRx; Namur, Belgium). Analytical quality of the assay was tested extensively by use of serum pools distributed over the whole plates to determine the intra- and inter-assay imprecision. The robustness of the nucleosomics biomarkers regarding variation in preanalytical sample handling factors was investigated prior to commencement of the study.

The team tested 90 patient samples and found significantly lower levels of nucleosomes containing methylated DNA in the blood of patients with colorectal cancer compared to healthy samples, and later validated the results in a second set of 113 people. The levels of nucleosome-bound methylated DNA were significantly decreased in CRC and BCD when compared to HC, although there was no difference between BCD and CRC.

Stefan Holdenrieder, MD, the lead author of the study said, “We are very excited to have our study published in such a prestigious journal. Since this study, we have seen more and more data confirming our findings and I am eager to ensure that this bank of research continues to grow so that patients can gain access to this rapid diagnostic tool as soon as possible. As such, I recently agreed to lead a performance evaluation study for VolitionRx's Conformité Européenne (CE) mark application process.” The study was published in the May 2014 issue of the journal Anticancer Research.

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University Hospital Bonn
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