1675P - Diagnostic performance of blood-based DNA methylation assay using epigenetic-specific peptide nucleic acid in pancreatic adenocarcinoma

Background

Pancreatic adenocarcinoma (PA) is an aggressive tumor with a poor prognosis and is difficult to diagnose with traditional tissue-based techniques. Cancer-associated DNA methylation biomarkers are promising for cancer diagnosis and have potential as non-invasive methods, as they can be detected not only in tissues but also in the blood. In the present study, we aimed to evaluate the diagnostic performance of a DNA methylation assay using epigenetic-specific peptide nucleic acid (Epi-sPNA) for PA.

Methods

An Epi-TOP pancreatic assay (Seasun Biomaterials, Daejeon, Korea) was used to detect PA-specific epigenetic and genetic biomarkers. The assay using Epi-sPNA enabled the accurate and quick analysis of methylation without sample processing using bisulfate. A total of 92gDNA samples collected from normal pancreatic and PA tissues of 46 patients who underwent surgical resection for PA were tested to evaluate the diagnostic performance of epigenetic biomarkers for PA. Further validation was performed on cell-free DNA isolated from the plasma samples of 10 individuals each from the PA, benign pancreatic disease, and normal groups.

Results

The combination of seven epigenetic biomarkers, HOXA9, TWIST, WT1, RPRM, BMP3, NPTX2, and BNC1 showed high sensitivity of 93.5% and specificity of 96.7% in discriminating between normal pancreatic and PA tissues. There were no significant differences in the methylation levels according to age, sex, or cancer stage. Plasma cell-free DNA collected from patients with PA and benign pancreatic disease and normal individuals was tested using a combination of epigenetic seven biomarkers with KRAS somatic mutations in codons 12, 13, and 61. Plasma-based DNA methylation analysis confirmed the diagnostic performance, with a sensitivity of 90.0%, specificity of 95.0%, and accuracy of 93.3%, whereas the accuracy of traditional serum biomarkers cancer antigen 19-9 and carcinoembryonic antigen was both 90.0%.

Conclusions

Our study suggests that seven differentially methylated genes, in combination with KRAS somatic mutations using Epi-TOP pancreatic assay, can be used as potential blood-based biomarkers for the diagnosis of PA.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Seasun Biomaterials, Daejeon, Korea.

Disclosure

All authors have declared no conflicts of interest.