Liquid biopsy, using a novel DNA methylation signature, distinguishes pancreatic adenocarcinoma from benign pancreatic disease

Lukas Vrba,Emmanuel Menashi,George S Watts,Hemanth Gavini,Charles Hu,Rachna T Shroff,Umamaheshwari Golconda,Mark A Nelson,Hytham Hammad,Daniel R Pennington,Denise J Roe,Marc Oshiro,Bernard W Futscher

doi:10.1186/s13148-022-01246-2

Lukas Vrba, Emmanuel Menashi + Show 11 more

Open Access

https://doi.org/10.1186/s13148-022-01246-2

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Abstract

We tested the ability of a novel DNA methylation biomarker set to distinguish metastatic pancreatic cancer cases from benign pancreatic cyst patients and to monitor tumor dynamics using quantitative DNA methylation analysis of cell-free DNA (cfDNA) from blood samples. The biomarkers were able to distinguish malignant cases from benign disease with high sensitivity and specificity (AUC = 0.999). Furthermore, the biomarkers detected a consistent decline in tumor-derived cfDNA in samples from patients undergoing chemotherapy. The study indicates that our liquid biopsy assay could be useful for management of pancreatic cancer patients.

Highlights

Pancreatic adenocarcinoma (PDAC) is a relatively rare disease (3% of all cancer cases) [1]; due to mostly late stage diagnosis, it has a 5-year survival rate of only 10% [2] and is the third leading cause of cancer death in the USA [1]
The liquid biopsy techniques are based on detecting tumor-specific biomarkers in cell-free DNA fraction of blood samples in which the circulating tumor DNA resides [7,8,9,10,11]; the ctDNA fraction varies based on tumor type and disease progression [12,13,14]
The biomarker DNA methylation signal was significantly increased in patients with liver metastasis and was able to distinguish them from PDAC patients without liver metastasis (AUC = 0.91, Additional file 1: Figure S2)

Summary

Introduction

Pancreatic adenocarcinoma (PDAC) is a relatively rare disease (3% of all cancer cases) [1]; due to mostly late stage diagnosis, it has a 5-year survival rate of only 10% [2] and is the third leading cause of cancer death in the USA [1]. One means to improve early pancreatic cancer detection and monitor disease burden during treatment could be a liquid biopsy approach. A liquid biopsy involves examining cancer-related material (i.e., DNA) from a blood sample. The liquid biopsy techniques are based on detecting tumor-specific biomarkers in cell-free DNA (cfDNA) fraction of blood samples in which the circulating tumor DNA (ctDNA) resides [7,8,9,10,11]; the ctDNA fraction varies based on tumor type and disease progression [12,13,14]. DNA methylation could be specific to tumors arising in different organs and tissues [11]. The detection of tumor-specific DNA methylation in cfDNA

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