Pancreatic cancer differential methylation atlas in blood, peri-carcinomatous and diseased tissue

Huan Wang, Fan Yin, Fang Yuan, Yuehua Men, Muhong Deng, Yang Liu, Qingfang Li


Background: Pancreatic cancer is common in elderly persons, and less than 20% of patients present with localized, potentially curable tumors.
Methods: We compared the methylated sites and genes in pericarcinous tissues compared to cancer tissue, and blood compared to pericarcinous tissues in order to harvest methylation markers for putative diagnostic and therapy monitoring purposes.
Results: Of 15,397 CpG sites detected in 7,440 genes, 5,605 (36.4%, 5,605 of 15,397) CpG sites were hypomethylated and 5,870 (38.12%, 5,870 of 15,397) CpG sites were hypermethylated. We then performed Gene Ontology (GO) and KEGG analysis to systematically characterize the ten significantly differentially methylated genes: PTPRN2, MAD1L1, TNXB, PRDM16, GNAS, KCNQ1, TSNARE1, HDAC4, TBCD, and DIP2C. Meanwhile, function analysis of genes with differentially methylated sites located in promoter regions of overlap group was also performed. According to previous studies, we further screened 22 pancreatic cancer related key genes. The results suggested that these key genes can influence methylation. GO and KEGG analysis indicated that these genes are involved in a wide range of functions.
Conclusions: The identification of differentially methylated genes in this study provides valuable information for liquid biopsy methylation markers in pancreatic cancer.