A Pilot Study of Blood-Based Methylation Markers Associated With Pancreatic Cancer

Abstract

Over the past several decades in the United States, incidence of pancreatic cancer (PCa) has increased, with the 5-year survival rate remaining extremely low at 10.8%. Typically, PCa is diagnosed at an advanced stage, with the consequence that there is more tumor heterogeneity and increased probability that more cells are resistant to treatments. Risk factors for PCa can serve as a way to select a high-risk population and develop biomarkers to improve early detection and treatment. We focus on blood-based methylation as an approach to identify a marker set that can be obtained in a minimally invasive way (through peripheral blood) and could be applied to a high-risk subpopulation [those with recent onset type 2 diabetes (DM)]. Blood samples were collected from 30 patients, 15 had been diagnosed with PCa and 15 had been diagnosed with recent onset DM. HumanMethylationEPIC Beadchip (Illumina, CA, United States) was used to quantify methylation of approximately 850,000 methylation sites across the genome and to analyze methylation markers associated with PCa or DM or both. Exploratory analysis conducted to propose importance of top CpG (5′—C—phosphate—G—3′) methylation site associated genes and visualized using boxplots. A methylation-based age predictor was also investigated for ability to distinguish disease groups from controls. No methylation markers were observed to be significantly associated with PCa or new onset diabetes compared with control the respective control groups. In our exploratory analysis, one methylation marker, CpG04969764, found in the Laminin Subunit Alpha 5 (LAMA5) gene region was observed in both PCa and DM Top 100 methylation marker sets. Modification of LAMA5 methylation or LAMA5 gene function may be a way to distinguish those recent DM cases with and without PCa, however, additional studies with larger sample sizes and different study types (e.g., cohort) will be needed to test this hypothesis.