AUTHOR=Kim Hongsik , Chu Jinah , Do In-Gu , Lee Yong-Pyo , Kim Hee Kyung , Yang Yaewon , Kwon Jihyun , Lee Ki Hyeong , Batochir Chinbayar , Jo Eunji , Kim Kyo Rim , Han Hye Sook 

TITLE=Novel diagnostic biomarkers for pancreatic cancer: assessing methylation status with epigenetic-specific peptide nucleic acid and KRAS mutation in cell-free DNA

JOURNAL=Frontiers in Oncology

VOLUME=14

YEAR=2024

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2024.1395473

DOI=10.3389/fonc.2024.1395473

ISSN=2234-943X

ABSTRACT=<sec><title>Purpose</title><p>Pancreatic ductal adenocarcinoma (PDAC) is an aggressive tumor with a poor prognosis that poses challenges for diagnosis using traditional tissue-based techniques. DNA methylation alterations have emerged as potential and promising biomarkers for PDAC. In this study, we aimed to assess the diagnostic potential of a novel DNA methylation assay based on epigenetic-specific peptide nucleic acid (Epi-sPNA) in both tissue and plasma samples for detecting PDAC.</p></sec><sec><title>Materials and methods</title><p>The study involved 46 patients with PDAC who underwent surgical resection. Epi-TOP pancreatic assay was used to detect PDAC-specific epigenetic biomarkers. The Epi-sPNA allowed accurate and rapid methylation analysis without bisulfite sample processing. Genomic DNA extracted from paired normal pancreatic and PDAC tissues was used to assess the diagnostic efficacy of epigenetic biomarkers for PDAC. Subsequent validation was conducted on cell-free DNA (cfDNA) extracted from plasma samples, with 10 individuals represented in each group: PDAC, benign pancreatic cystic neoplasm, and healthy control.</p></sec><sec><title>Results</title><p>The combination of seven epigenetic biomarkers (<italic>HOXA9, TWIST, WT1, RPRM, BMP3, NPTX2</italic>, and <italic>BNC1</italic>) achieved 93.5% sensitivity and 96.7% specificity in discerning normal pancreatic from PDAC tissues. Plasma cfDNA, analyzed using these markers and <italic>KRAS</italic> mutations, exhibited a substantial 90.0% sensitivity, 95.0% specificity, and an overall 93.3% accuracy for discriminating PDAC. Notably, cancer antigen 19-9 and carcinoembryonic antigen both had an accuracy of 90.0%.</p></sec><sec><title>Conclusion</title><p>Our study suggests that analyzing seven differentially methylated genes with <italic>KRAS</italic> mutations in cfDNA using the novel Epi-TOP pancreatic assay is a potential blood-based biomarker for the diagnosis of PDAC.</p></sec>