Abstract

Abnormalities of DNA modifications is closely related to the pathogenesis and prognosis of pancreatic cancer. The development of third-generation sequencing technology has brought opportunities for the study of new epigenetic modification in cancer. Here, we screened the N6-methyladenine (6mA) and 5-methylcytosine (5mC) modification in pancreatic cancer based on Oxford Nanopore Technologies (ONT) sequencing. Compared with 5mC modifications, the methylation level of 6mA modifications were lower and upregulated in cancer tissues. We developed a novel method to define differentially methylated deficient region (DMDR) which mapped 1319 protein-coding genes in pancreatic cancer. Genes screened by DMDRs were more significant enriched in the cancer genes compared with the traditional differential methylation method (p < 0.001 vs. p = 0.21, hypergeometric test). Functional enrichment analysis indicated that 891 genes were closely related to alternative splicing. Multi-omics data from TCGA showed that these genes were frequently altered in cancer samples and 7 genes with high expression (ADAM9, ADAM10, EPS8, FAM83A, FAM111B, LAMA3 and TES) were significantly associated with poor prognosis. In addition, the distinction for pancreatic cancer subtypes were used 46 subtype-specific genes and unsupervised clustering. Overall, our study is the first to explore the molecular characteristics of 6mA modifications in pancreatic cancer, indicating that 6mA have the potential to be a target for future clinical treatment.

Pancreatic cancer samples and processing