Aberrant DNA methylation is often involved in
carcinogenesis. Our initial goal was to identify DNA methylation
biomarkers associated with
pancreatic cancer. A genomewide methylation study was performed on
DNA from pancreatic ductal
adenocarcinoma (PDAC) and endocrine pancreas
tumors. Validation of DNA methylation patterns and concomitant alterations in expression of gene candidates was performed on patient samples and
pancreatic cancer cell lines. Furthermore, validation was done on independent data from The
Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Finally, droplet digital PCR was employed to detect DNA methylation marks in cell-free (cf)
DNA isolated from plasma samples of PDAC patients and
cancer-free blood donors. Hypermethylation of the SST gene (encoding
somatostatin) and concomitant downregulation of its expression were discovered in PDAC and endocrine
tumor tissues while not being present in
chronic pancreatitis (inflamed) tissues and normal pancreas. Fittingly, treatment with a
somatostatin agonist (
octreotide) reduced cell proliferation and migration of
pancreatic cancer cells. Diagnostic performance of SST methylation in a receiver operating characteristic curve analysis was 100% and 89% for tissue and plasma samples, respectively. A large body of TCGA and GEO data confirmed SST hypermethylation and downregulation in PDAC and showed a similar effect in a broad spectrum of other
tumor entities. SST promoter methylation represents a sensitive and promising molecular, pan-
cancer biomarker detectable in
tumor tissue, and liquid biopsy samples.