DNA Hypermethylation as a Blood-Based Marker for Pancreatic Cancer: A Literature Review.
OBJECTIVE
The aim is to review genes aberrantly methylated in pancreatic cancer. This review focuses on DNA promoter hypermethylation in plasma and serum to describe the most promising genes that may be useful as minimally invasive diagnostic blood-based markers for pancreatic cancer.


METHODS
A systematic search of the literature was performed using the PubMed and EMBASE databases. The following MeSH terms and free text were used: pancreatic disease, pancreatic cancer, pancreatic neoplasm, methylation, DNA hypermethylation, CG rich sequence, CpG island, cell-free DNA, blood, plasma, serum, fluids, and secretions.


RESULTS
In total, 720 articles were found. Eight studies on cell-free DNA promoter hypermethylation in plasma or serum and 2 studies on hypermethylation in whole blood/leukocyte DNA from patients with pancreatic cancer were identified. The search for a hypermethylated marker in cell-free DNA is characterized by a few small studies lacking well-defined control groups. No single gene has been identified as a diagnostic marker.


CONCLUSIONS
Because of insufficient power, none of the genes examined have the potential to work as an individual diagnostic marker, suggesting that a panel of several genes is needed. Further research is warranted before a blood-based diagnostic marker for pancreatic cancer based on promoter hypermethylation can be applied clinically.
From the Departments of *Gastrointestinal Surgery and †Clinical Biochemistry and Molecular Diagnostics, Aalborg University Hospital, Aalborg, Denmark.
Stine Dam
SD
Henriksen
Poul Henning
PH
Madsen
Henrik
H
Krarup
Ole
O
Thorlacius-Ussing
D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics*; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D010190:Pancreatic Neoplasms / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012680:Sensitivity and Specificity
D014408:Biomarkers, Tumor