Abstract
As one of the most malicious cancers, pancreatic cancer is difficult to treat due to the lack of effective early diagnosis. Therefore, it is urgent to find reliable diagnostic and predictive markers for the early detection of pancreatic cancer. In recent years, the detection of circulating cell-free DNA (cfDNA) methylation in plasma has attracted global attention for non-invasive and early cancer diagnosis. Here, we carried out a genome-wide cfDNA methylation profiling study of pancreatic ductal adenocarcinoma (PDAC) patients by methylated DNA immunoprecipitation coupled with high-throughput sequencing (MeDIP-seq). Compared with healthy individuals, 775 differentially methylated regions (DMRs) located in promoter regions were identified in PDAC patients with 761 hypermethylated and 14 hypomethylated regions; meanwhile, 761 DMRs in CpG islands (CGIs) were identified in PDAC patients with 734 hypermethylated and 27 hypomethylated regions (p-value < 0.0001). Then, 143 hypermethylated DMRs were further selected which were located in promoter regions and completely overlapped with CGIs. After performing the least absolute shrinkage and selection operator (LASSO) method, a total of eight markers were found to fairly distinguish PDAC patients from healthy individuals, including TRIM73, FAM150A, EPB41L3, SIX3, MIR663, MAPT, LOC100128977, and LOC100130148. In conclusion, this work identified a set of eight differentially methylated markers that may be potentially applied in non-invasive diagnosis of pancreatic cancer.
Highlights
Pancreatic ductal adenocarcinoma (PDAC) is one of the most highly aggressive diseases in the world
By MeDIP-seq analysis, we compared the differentially methylated regions (DMRs) of PDAC cell-free DNA (cfDNA) with that of normal control, and identified 143 hypermethylated DMRs which were located in promoter regions and completely overlapped with CpG islands (CGIs) in PDAC patients
After cross-validation with publicly available DNA methylation data, including 339 pancreatic adenocarcinoma (PAAD) patients and 357 normal controls, we successfully identified eight probes from six differentially methylated genes, containing TRIM73, FAM150A, EPB41L3, SIX3, MIR663, MAPT, LOC100128977, and LOC100130148, which could be used as potential biomarkers for early detection for PDAC patients
Summary
Pancreatic ductal adenocarcinoma (PDAC) is one of the most highly aggressive diseases in the world. Due to the hard challenge of detecting the disease at an early stage, poor prognosis often occurs. The morbidity of PDAC is approximately close to that of mortality. 80% of PDAC patients have no early symptoms before the advanced stage (Kaur et al, 2012) with a 5-year survival rate as low as 9% (Siegel et al, 2019). PDAC is the fourth leading cause of cancerrelated death worldwide and is predicted to rise to second place by 2030 (Rahib et al, 2014). Ultrasonography, computed tomography, positron emission tomography, magnetic
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