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. 2016:2016:2192853.
doi: 10.1155/2016/2192853. Epub 2016 Jul 14.

Discovery and Validation of Hypermethylated Markers for Colorectal Cancer

Jiufeng Wei  1 , Guodong Li  1 , Shuwei Dang  1 , Yuhui Zhou  1 , Kai Zeng  1 , Ming Liu  1
Affiliations

Discovery and Validation of Hypermethylated Markers for Colorectal Cancer

Jiufeng Wei et al. Dis Markers. 2016.

Abstract

Colorectal carcinoma (CRC) is one of the most prevalent malignant tumors worldwide. Screening and early diagnosis are critical for the clinical management of this disease. DNA methylation changes have been regarded as promising biomarkers for CRC diagnosis. Here, we map DNA methylation profiling on CRC in six CRCs and paired normal samples using a 450 K bead array. Further analysis confirms the methylation status of candidates in two data sets from the Gene Expression Omnibus. Receiver operating characteristic (ROC) curves are calculated to determine the diagnostic performances. We identify 1549 differentially methylated regions (DMRs) showing differences in methylation between CRC and normal tissue. Two genes (ADD2 and AKR1B1), related to the DMRs, are selected for further validation. ROC curves show that the areas under the curves of ADD2 and AKR1B1 are higher than that of SEPT9, which has been clinically used as a screening biomarker of CRC. Our data suggests that aberrant DNA methylation of ADD2 and AKR1B1 could be potential screening markers of CRC.

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Figures

Figure 1
Figure 1
Distribution of DMRs in the human CRC genome. (a) Stacked bar charts showing the distribution of the hypermethylated DMRs over five gene categories: promoter, 5′UTR, 1st exon, gene body, 3′UTR, and intergenic regions. (b) Stacked bar charts showing the distribution of the hypomethylated DMRs over five gene categories: promoter, 5′UTR, 1st exon, gene body, 3′UTR, and intergenic regions. (c) Bar charts showing the distribution of the hypermethylated and hypomethylated DMRs considering four sizes: 1–400 bp, 401–800 bp, 801–1200 bp, and >1200 bp.
Figure 2
Figure 2
The different methylation levels of three genes in normal tissue, adenoma, and CRC. (a) The strip plot shows the different methylation levels of three genes (SEPT9, ADD2, and AKR1B1) in normal tissue and CRC with the data set GSE68060 from GEO. (b) The strip plot shows the different methylation level of three genes (SEPT9, ADD2, and AKR1B1) in normal tissue, adenoma, and CRC with the data set GSE48684 from GEO.
Figure 3
Figure 3
ROC curves of ADD2/AKR1B1/SEPT9 methylation using the data sets GSE48684 and GSE68060. (a) and (b) Receiver operating characteristic (ROC) curve showing accurate discrimination based on ADD2/AKR1B1/SEPT9 methylation using the data set GSE48684. (a) Between normal tissue and CRC tissue samples. (b) Between normal tissue and adenoma + CRC tissue samples. (c) ROC curve showing accurate discrimination based on ADD2/AKR1B1/SEPT9 methylation between normal tissue and CRC tissue samples using the data set GSE68060.
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