Abstract
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.
Highlights
Colorectal carcinoma(CRC) is the third most common malignancy throughout the world [1]
Global statistics showed that in 2012 alone, over 1.36 million people were diagnosed with colorectal carcinoma, and approximately 693,900 people died from this disease [2]
We demonstrated that the methylation status of GFRA1 and GSTM2 could be used as potential biomarkers for the screening of rectal cancer
Summary
Colorectal carcinoma(CRC) is the third most common malignancy throughout the world [1]. Global statistics showed that in 2012 alone, over 1.36 million people were diagnosed with colorectal carcinoma, and approximately 693,900 people died from this disease [2]. Rectal cancers are reported to represent approximately 33% of CRC diagnoses [1]. The diagnosis of rectal cancer is primarily determined based on the clinical data and pathological analysis of patients [3]. Successful early detection of rectal cancer patients is still hampered by the lack of highly sensitive and specific biomarkers. The identification of biomarkers, including molecular biomarkers, for patient screening and early detection of CRC rectal cancer is a high priority
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