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Functional characteristics of DNA N6-methyladenine modification based on long-read sequencing in pancreatic cancer.
- Source :
-
Briefings in Functional Genomics . Mar2024, Vol. 23 Issue 2, p150-162. 13p. - Publication Year :
- 2024
-
Abstract
- Abnormalities of DNA modifications are 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 sequencing. The 6mA levels were lower compared with 5mC and upregulated in pancreatic cancer. We developed a novel method to define differentially methylated deficient region (DMDR), which overlapped 1319 protein-coding genes in pancreatic cancer. Genes screened by DMDRs were more significantly enriched in the cancer genes compared with the traditional differential methylation method (P < 0.001 versus P = 0.21, hypergeometric test). We then identified a survival-related signature based on DMDRs (DMDRSig) that stratified patients into high- and low-risk groups. Functional enrichment analysis indicated that 891 genes were closely related to alternative splicing. Multi-omics data from the cancer genome atlas showed that these genes were frequently altered in cancer samples. Survival analysis indicated that seven 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 was determined using 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 has the potential to be a target for future clinical treatment. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 20412649
- Volume :
- 23
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Briefings in Functional Genomics
- Publication Type :
- Academic Journal
- Accession number :
- 176151815
- Full Text :
- https://doi.org/10.1093/bfgp/elad021