Unraveling the clinical impact of differential DNA methylation in PDAC: A systematic review

Despite significant efforts to improve clinical outcomes, pancreatic ductal adenocarcinoma (PDAC) has a high mortality rate. The poor prognosis associated with this disease is multifactorial and associated with a highly variable genetic profile associated with its pathogenesis. Epigenetic modifications including DNA methylation further affect the expression of genetic material. However, there is no comprehensive understanding of the clinical impact of DNA methylation in PDAC.

A systematic literature review was registered on the International Prospective Register of Systematic Reviews database (CRD42023451955) and followed Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. An electronic search was conducted using the following databases: CINAHL Plus, Cochrane Library, Embase, Web of Science, Ovid Medline, and Google Scholar. Inclusion criteria included studies of patients with a PDAC diagnosis and information regarding genes or CpG sites that potentially affect diagnosis, prognosis, or survival of PDAC.

The initial search retrieved 2402 articles, and 423 duplicates were excluded. After exclusion criteria was applied, 19 studies were included. The most common genes recorded as affecting tumor pathogenesis were SFRP1 (n = 3/19, 15.7 %) and NPTX2 (n = 2/19, 10,5 %). Studies indicated that hypermethylation of SFRP1 and NPTX2 were associated with poor prognosis.

PDAC is associated with a range of epigenetic modifications. Methylation of specific genes related to PDAC may influence survival and prognosis and be a therapeutic target. Individual patient epigenetic analysis may be a future direction in directing PDAC treatment and prognosis.