Cell-free DNA promoter hypermethylation in plasma as a predictive marker for survival of patients with pancreatic adenocarcinoma

Abstract

IntroductionFew prognostic biomarkers are available for pancreatic cancer. The aim of this study is to examine the correlation between the survival of pancreatic adenocarcinoma patients and hypermethylated genes in plasma-derived cell-free DNA.MethodsConsecutive patients with pancreatic adenocarcinoma were prospectively included and staged according to the TNM classification. Methylation-specific PCR of 28 genes was conducted. A survival prediction model independent of cancer stage and stage-specific survival prediction models were developed by multivariable Cox regression analysis using backward stepwise selection.ResultsNinety-five patients with pancreatic adenocarcinoma were included. Patients with more than 10 hypermethylated genes had a HR of 2.03 (95% CI; 1.15-3.57) compared to patients with fewer hypermethylated genes. Three survival prediction models were developed: Total group; (American Society of Anesthesiologists score (ASA)=3, GSTP1, SFRP2, BNC1, SFRP1, TFPI2, and WNT5A) Risk groups 2, 3 and 4 had a HR of 2.65 (95% CI; 1.24-5.66), 4.34 (95% CI; 1.98-9.51) and 21.19 (95% CI; 8.61-52.15), respectively, compared to risk group 1. Stage I-II; (ASA=3, SFRP2, and MESTv2) Risk groups 2, 3 and 4 had a HR of 4.83 (95% CI; 2.01-11.57), 9.12 (95% CI; 2.18-38.25) and 70.90 (95% CI; 12.63-397.96), respectively, compared to risk group 1. Stage IV; (BMP3, NPTX2, SFRP1, and MGMT) Risk group 2 had a HR of 5.23 (95% CI; 2.13-12.82) compared to risk group 1.ConclusionPrediction models based on cell-free DNA hypermethylation stratified pancreatic adenocarcinoma patients into risk groups according to survival. The models have the potential to work as prognostic biomarkers. However, further validation of the results is required to substantiate the findings.

Liquid Biopsy Approach for Pancreatic Ductal Adenocarcinoma

“…Numerous studies have been conducted to investigate the role of circulating DNA in patients with PDAC. The major studies that included more than 20 patients are compiled in Table 2 [55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,85]. Of the 24 studies, only 13 included patients with benign pancreatic lesions or healthy subjects.…”

Circulating Tumor Cells and Cell-Free DNA in Pancreatic Ductal Adenocarcinoma

“…A diagnostic prediction model was able to differentiate between PDAC and benign disease, with a sensitivity of 76% and a specificity of 83%. 65…”

Impact of circulating tumor DNA in hepatocellular and pancreatic carcinomas

“…CfDNA promotor hypermethylation in plasma or serum could be detected in all stages of PC (Henriksen et al 2017b). Henriksen et al developed a survival prediction model based on plasma-derived cfDNA hypermethylation of a large gene panel that enables the stratification of patients into risk groups (Henriksen et al 2017a). Further methylation analyses of ctDNA were able to differentiate PC from chronic pancreatitis and healthy controls (Henriksen et al 2016;Liggett et al 2010;Melnikov et al 2009;Melson et al 2014;Park et al 2012).…”