Integrated analysis of genome-wide DNA methylation and gene expression profiles identifies potential novel biomarkers of rectal cancer
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Jiufeng Wei1,2,*, Guodong Li1,2,*, Jinning Zhang1,2, Yuhui Zhou1,2, Shuwei Dang1,2, Hongsheng Chen1,2, Qiong Wu3, Ming Liu1,2
1Department of General Surgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, 150001, P.R. China
2Bio-Bank of Department of General Surgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, 150001, P.R. China
3School of Life Science and Technology, State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin, 150001, P.R. China
*These authors have contributed equally as first authors
Qiong Wu, email: [email protected]
Ming Liu, email: [email protected]
Keywords: DNA methylation, epigenetics, gene expression array, rectal carcinoma, molecular marker
Received: January 26, 2016 Accepted: August 8, 2016 Published: August 23, 2016
DNA methylation was regarded as the promising biomarker for rectal cancer diagnosis. However, the optimal methylation biomarkers with ideal diagnostic performance for rectal cancer are still limited. To identify new molecular markers for rectal cancer, we mapped DNA methylation and transcriptomic profiles in the six rectal cancer and paired normal samples. Further analysis revealed the hypermethylated probes in cancer prone to be located in gene promoter. Meanwhile, transcriptome analysis presented 773 low-expressed and 1,161 over-expressed genes in rectal cancer. Correction analysis identified a panel of 36 genes with an inverse correlation between methylation and gene expression levels, including 10 known colorectal cancer related genes. From the other 26 novel marker genes, GFRA1 and GSTM2 were selected for further analysis on the basis of their biological functions. Further experiment analysis confirmed their methylation and expression status in a larger number (44) of rectal cancer samples, and ROC curves showed higher AUC than SEPT9, which has been used as a biomarker in rectal cancer. Our data suggests that aberrant DNA methylation of contiguous CpG sites in methylation array may be potential diagnostic markers of rectal cancer.
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