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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.

Integrated analysis of genome-wide DNA methylation and gene expression profiles identifies potential novel biomarkers of rectal cancer