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Identification of an epigenetic biomarker panel with high sensitivity and specificity for colorectal cancer and adenomas

DOI: 10.1186/1476-4598-10-85

Keywords: Biomarker, CNRIP1, colorectal neoplasia, early detection, FBN1, INA, MAL, methylation, SNCA, SPG20

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Abstract:

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.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.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.Colorectal cancer is the third most common cancer type in the US and is a major contributor to cancer-death [1]. Most cases of colorectal cancer develop from benign precursors (adenomas) during a long time interval. This provides a good opportunity for detection of colorectal cancer at an early curable stage and to screen for potentially pre-malignant adenomas [2]. Both flexible sigmoidoscopy and the Fecal Occult Blood Test (FOBT) have been tested in randomized trials and shown to reduce mortality from colorectal cancer [3]. By sigmoidoscopy adenomas may be detected and removed and thus the incidence of cancer will be reduced [4], however, this screening is invasive and cumbersome for the patient. FOBT on the other hand is non-invasive and currently the most commonly used screening test for colorectal cancer in Europe. Although the sensitivity and specificity measurements of FOBT have been

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