TBA (21W147)

Multi-Omic Profiling Of Pancreatic Cyst Fluid For The Identification Of A Novel Biomarker Panel Of Patient Cancer Risk

Author(s)

Kane, L.E. (1) Mellotte, G.S. (2) Marcone, S. (1) Ridgway, P.F.(3) Conlon, K.C. (4) Ryan, B.M. (2) Maher, S.G. (1)

Department(s)/Institutions

1 Department of Surgery, Trinity St. James’s Cancer Institute, St. James's Hospital, Dublin 8 2 Department of Gastroenterology, Tallaght University Hospital, Dublin 24 3 Upper Gastrointestinal Surgery Department, Trinity College Dublin, Tallaght University Hospital, Dublin 24 4 Discipline of Surgery, School of Medicine, Trinity College Dublin, Dublin 2

Introduction

Pancreatic cancer was responsible for almost 500,000 deaths globally in 2020 according to GLOBOCAN. Pancreatic cystic lesions are fluid-filled protrusions either on or inside the pancreas, which can either be benign or pre-malignant. Current guidelines to stratify patients based on risk are imperfect.

Aims/Background

Multi-omic profiling of the fluid within pancreatic cysts could aid in the identification of a novel biomarker panel of patient cancer risk.

Method

Pancreatic cyst fluid (PCF) was collected from 40 patients by EUS-FNA. Patients were stratified using the 2018 European evidence-based guidelines into low-risk, high risk and no-risk or pseudocyst. PCF was sonicated and subsequently processed using SP3 paramagnetic beads prior to LC-MS. MS-generated data were analysed in Perseus (v1.6.13.0). HTG microRNA whole transcriptome sequencing was run on whole PCF with 3 post-sequencing quality control metrics. MiRNA sequencing data were analysed using HTG EdgeSeq Reveal (v3.1.0).

Results

MS-analysis of PCF samples revealed eight proteins to be significantly upregulated in high-risk PCF compared to low-risk (p<0.05, FDR=0.05, s0=0.1). Whole transcriptome sequencing revealed forty-six miRNAs were significantly upregulated in high-risk PCF compared to low-risk (adj-p<0.05, FDR=0.05, s0=0.1). Differentially expressed proteins and miRNAs are currently being technically validated by ELISA and qPCR respectively. They will then be examined in matched patient serum with the aim of generating a less invasive predictive biomarker panel for patient risk.

Conclusions

Multi-omic profiling of pancreatic cyst fluid provides an abundance of potential biomarkers of patient risk. Interrogation of these factors in patient serum could present a novel blood-based multi-marker panel for less invasive patient risk stratification.