[show abstract][hide abstract] ABSTRACT: Cholangiocarcinoma is notoriously difficult to diagnose, and the mortality rate is high due to late clinical presentation. CpG island promoter methylation is frequently seen in cancer development. In the present study, we aimed at identifying novel epigenetic biomarkers with the potential to improve the diagnostic accuracy of cholangiocarcinoma. Microarray data analyses of cholangiocarcinoma cell lines treated with epigenetic drugs and their untreated counterparts were compared with previously published gene expression profiles of primary tumors and with non-malignant controls. Genes responding to the epigenetic treatment that were simultaneously downregulated in primary cholangiocarcinoma compared with controls (n = 43) were investigated for their promoter methylation status in cancer cell lines from the gastrointestinal tract. Genes commonly methylated in cholangiocarcinoma cell lines were subjected to quantitative methylation-specific polymerase chain reaction in a total of 93 clinical samples (cholangiocarcinomas and non-malignant controls). CDO1, DCLK1, SFRP1 and ZSCAN18, displayed high methylation frequencies in primary tumors and were unmethylated in controls. At least one of these four biomarkers was positive in 87% of the tumor samples, with a specificity of 100%. In conclusion, the novel methylation-based biomarker panel showed high sensitivity and specificity for cholangiocarcinoma. The potential of these markers in early diagnosis of this cancer type should be further explored.
Epigenetics: official journal of the DNA Methylation Society 09/2012; 7(11). · 4.58 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.
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.
Molecular Cancer 07/2011; 10:85. · 5.13 Impact Factor