A novel sensitive detection method for DNA methylation in circulating free DNA of pancreatic cancer

PloS One
Keiko ShinjoYutaka Kondo

Abstract

Despite recent advances in clinical treatment, pancreatic cancer remains a highly lethal malignancy. In order to improve the survival rate of patients with pancreatic cancer, the development of non-invasive diagnostic methods using effective biomarkers is urgently needed. Here, we developed a highly sensitive method to detect DNA methylation in cell-free (cf)DNA samples based on the enrichment of methyl-CpG binding (MBD) protein coupled with a digital PCR method (MBD-ddPCR). Five DNA methylation markers for the diagnosis of pancreatic cancer were identified through DNA methylation microarray analysis in 37 pancreatic cancers. The sensitivity and specificity of the five markers were validated in another independent cohort of pancreatic cancers (100% and 100%, respectively; n = 46) as well as in The Cancer Genome Atlas data set (96% and 90%, respectively; n = 137). MBD-ddPCR analysis revealed that DNA methylation in at least one of the five markers was detected in 23 (49%) samples of cfDNA from 47 patients with pancreatic cancer. Further, a combination of DNA methylation markers and the KRAS mutation status improved the diagnostic capability of this method (sensitivity and specificity, 68% and 86%, respectively). Genome-wide MBD-...Continue Reading

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Citations

Feb 23, 2021·Frontiers in Cell and Developmental Biology·Aitor Rodriguez-CasanovaAngel Diaz-Lagares
Aug 28, 2021·Biomolecules·Sarah S WangChang-Il Hwang

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Methods Mentioned

BETA
methylation
PCR
biopsy
pull down
MBD-seq

Clinical Trials Mentioned

NCT02889978

Software Mentioned

HOMER
bedGraph
Integrative Genome Viewer ( IGV )
GraphPad
GraphPad Prism
Bioanalyzer
deepTools2
JMP
igvtools

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