Non-Invasive Characterization of the Pancreas During Bariatric Surgery via Circulating Pancreatic Specific Cell-free Messenger RNA

Abstract

Bariatric surgery results in sustained weight loss and improvement in glucose homeostasis. However, the lack of accessible non-invasive tools to examine molecular alterations occurring in the pancreas limits our understanding of the causes and recovery of glucose homeostasis. Here, we describe the use of a circulating cell free mRNA (cfmRNA) based multiplex qPCR assay to selectively amplify and quantify circulating pancreatic specific transcripts levels within plasma. We applied this assay to a cohort of 58 plasma samples consisting of 10 patients that tracks multiple time points including pre and post-bariatric surgery. In our targeted multiplex screen of 14 selected pancreatic specific circulating transcripts, we identified 13 pancreatic specific transcripts that can be amplified from plasma. Furthermore, when quantifying the amplicons obtained in the short-term post-surgery (2 weeks-1 month) and long-term (3-12 months), we observed a consistent reduction of circulating GCG transcripts during short term post-surgery. Across the cohort, GCG cfmRNA levels correlated significantly with common metrics of improvement following bariatric surgery such as: haemoglobin A1c levels (R: -0.41, p-value: 0.0039) and percentage of excess weight loss (R: 0.29, p-value: 0.046).

Keywords: bariatric surgery; cfmRNA; liquid biospsy; metabolic health; pancreas.