Research
Identification of an epigenetic biomarker panel with high sensitivity and specificity for colorectal cancer and adenomas
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* Corresponding author: Ragnhild A Lothe rlothe@rr-research.no
1 Department of Cancer Prevention, Institute for Cancer Research, Oslo University Hospital - Radiumhospitalet, Oslo, Norway
2 Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway
3 Surgical Department, Oslo University Hospital - Aker Hospital, Oslo, Norway
4 Institute of Forensic Medicine, University of Oslo, Norway
5 Faculty of Medicine, University of Oslo, Oslo, Norway
6 Department of Medicine Division of Gastroenterology, Telemark Hospital, Skien, Norway
7 The Cancer Registry of Norway, Oslo, Norway
8 Department of Gastroenterology, Oslo University Hospital, Oslo, Norway
9 Department for organ transplantation, gastroenterology and nephrology, Oslo University Hospital - Rikshospitalet, Oslo, Norway
10 Research Center, Akershus University Hospital, Lørenskog, Norway
Molecular Cancer 2011, 10:85 doi:10.1186/1476-4598-10-85
Published: 21 July 2011Abstract
Background
The presence of cancer-specific DNA methylation patterns in epithelial colorectal cells in human feces provides the prospect of a simple, non-invasive screening test for colorectal cancer and its precursor, the adenoma. This study investigates a panel of epigenetic markers for the detection of colorectal cancer and adenomas.
Methods
Candidate biomarkers were subjected to quantitative methylation analysis in test sets of tissue samples from colorectal cancers, adenomas, and normal colonic mucosa. All findings were verified in independent clinical validation series. A total of 523 human samples were included in the study. Receiver operating characteristic (ROC) curve analysis was used to evaluate the performance of the biomarker panel.
Results
Promoter hypermethylation of the genes CNRIP1, FBN1, INA, MAL, SNCA, and SPG20 was frequent in both colorectal cancers (65-94%) and adenomas (35-91%), whereas normal mucosa samples were rarely (0-5%) methylated. The combined sensitivity of at least two positives among the six markers was 94% for colorectal cancers and 93% for adenoma samples, with a specificity of 98%. The resulting areas under the ROC curve were 0.984 for cancers and 0.968 for adenomas versus normal mucosa.
Conclusions
The novel epigenetic marker panel shows very high sensitivity and specificity for both colorectal cancers and adenomas. Our findings suggest this biomarker panel to be highly suitable for early tumor detection.