Projection of Epigenetic Markers of Type 2 Diabetes Reveal Pancreatic Cancer Prognostic Tumour States

Abstract

Type 2 diabetes (T2D) and Pancreatic Duct Carcinoma (PDAC), are two diseases with a chronic metabolic disorder related to a deregulated cellular energy metabolism, insulin resistance and an increased inflammatory reaction within the organism. T2D Literature suggests that the metabolic dysregulations related to T2D are known to be implicated in the progression of PDAC, yet it is unclear whether the epigenetic alterations associated with T2D are similarly altered in pancreatic tumours. In this study, we introduce a novel cross-disease epigenomic framework to quantify T2D-associated DNA methylation patterns within PDAC. Using this epigenomic framework, we found that there was considerable inter-tumoural heterogeneity of epigenetics relating to T2D. PDAC tumours that had high T2D methylation scores exhibited consistent methylation patterns, suggesting a communal T2D ”signature”, and they also demonstrated significantly less survival than their counterparts. In Cox proportional hazards models of the entire sample, there was a significant increase in mortality associated with increasing T2D methylation score. The findings support that T2D-associated epigenetic dysregulation has potential clinical relevance to pancreatic tumours. The study provides an interpretable and scalable method for cross-disease epigenomic projection, which provides new insight into the relationship between metabolic and epigenetic alteration in PDAC.