Multi-omic biomarker panel in pancreatic cyst fluid and serum predicts patients at a high risk of pancreatic cancer development

Abstract Integration of multi-omic data for the purposes of biomarker discovery can provide novel and robust panels across multiple biological compartments. Appropriate analytical methods are key to ensuring accurate and meaningful outputs in the multi-omic setting. Here, we extensively profile the...

Full description

Saved in:
Bibliographic Details
Main Authors: Laura E. Kane, Gregory S. Mellotte, Eimear Mylod, Paul Dowling, Simone Marcone, Caitriona Scaife, Elaine M. Kenny, Michael Henry, Paula Meleady, Paul F. Ridgway, Finbar MacCarthy, Kevin C. Conlon, Barbara M. Ryan, Stephen G. Maher
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Scientific Reports
Subjects:
Online Access:https://doi.org/10.1038/s41598-024-83742-4
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1841559774916771840
author Laura E. Kane
Gregory S. Mellotte
Eimear Mylod
Paul Dowling
Simone Marcone
Caitriona Scaife
Elaine M. Kenny
Michael Henry
Paula Meleady
Paul F. Ridgway
Finbar MacCarthy
Kevin C. Conlon
Barbara M. Ryan
Stephen G. Maher
author_facet Laura E. Kane
Gregory S. Mellotte
Eimear Mylod
Paul Dowling
Simone Marcone
Caitriona Scaife
Elaine M. Kenny
Michael Henry
Paula Meleady
Paul F. Ridgway
Finbar MacCarthy
Kevin C. Conlon
Barbara M. Ryan
Stephen G. Maher
author_sort Laura E. Kane
collection DOAJ
description Abstract Integration of multi-omic data for the purposes of biomarker discovery can provide novel and robust panels across multiple biological compartments. Appropriate analytical methods are key to ensuring accurate and meaningful outputs in the multi-omic setting. Here, we extensively profile the proteome and transcriptome of patient pancreatic cyst fluid (PCF) (n = 32) and serum (n = 68), before integrating matched omic and biofluid data, to identify biomarkers of pancreatic cancer risk. Differential expression analysis, feature reduction, multi-omic data integration, unsupervised hierarchical clustering, principal component analysis, spearman correlations and leave-one-out cross-validation were performed using RStudio and CombiROC software. An 11-feature multi-omic panel in PCF [PIGR, S100A8, REG1A, LGALS3, TCN1, LCN2, PRSS8, MUC6, SNORA66, miR-216a-5p, miR-216b-5p] generated an AUC = 0.806. A 13-feature multi-omic panel in serum [SHROOM3, IGHV3-72, IGJ, IGHA1, PPBP, APOD, SFN, IGHG1, miR-197-5p, miR-6741-5p, miR-3180, miR-3180-3p, miR-6782-5p] produced an AUC = 0.824. Integration of the strongest performing biomarkers generated a 10-feature cross-biofluid multi-omic panel [S100A8, LGALS3, SNORA66, miR-216b-5p, IGHV3-72, IGJ, IGHA1, PPBP, miR-3180, miR-3180-3p] with an AUC = 0.970. Multi-omic profiling provides an abundance of potential biomarkers. Integration of data from different omic compartments, and across biofluids, produced a biomarker panel that performs with high accuracy, showing promise for the risk stratification of patients with pancreatic cystic lesions.
format Article
id doaj-art-e5da0fa21ee146faab413210368b6a72
institution Kabale University
issn 2045-2322
language English
publishDate 2025-01-01
publisher Nature Portfolio
record_format Article
series Scientific Reports
spelling doaj-art-e5da0fa21ee146faab413210368b6a722025-01-05T12:14:16ZengNature PortfolioScientific Reports2045-23222025-01-0115111610.1038/s41598-024-83742-4Multi-omic biomarker panel in pancreatic cyst fluid and serum predicts patients at a high risk of pancreatic cancer developmentLaura E. Kane0Gregory S. Mellotte1Eimear Mylod2Paul Dowling3Simone Marcone4Caitriona Scaife5Elaine M. Kenny6Michael Henry7Paula Meleady8Paul F. Ridgway9Finbar MacCarthy10Kevin C. Conlon11Barbara M. Ryan12Stephen G. Maher13Department of Surgery, Trinity St. James’s Cancer Institute, Trinity Translational Medicine Institute, Trinity College Dublin, St. James’s HospitalDepartment of Gastroenterology, Tallaght University HospitalDepartment of Surgery, Trinity St. James’s Cancer Institute, Trinity Translational Medicine Institute, Trinity College Dublin, St. James’s HospitalDepartment of Biology, Maynooth UniversityDepartment of Surgery, Trinity St. James’s Cancer Institute, Trinity Translational Medicine Institute, Trinity College Dublin, St. James’s HospitalMass Spectrometry Facility, Conway Institute of Biomolecular and Biomedical Research, University College DublinELDA BiotechNational Institute for Cellular Biotechnology, Dublin City UniversityNational Institute for Cellular Biotechnology, Dublin City UniversityDepartment of Surgery, Centre for Pancreatico-Biliary Diseases, Trinity College Dublin, St. James’s HospitalDepartment of Clinical Medicine, Trinity Translational Medicine Institute, Trinity College Dublin, St. James’s HospitalDepartment of Surgery, School of Medicine, Trinity College DublinDepartment of Gastroenterology, Tallaght University HospitalDepartment of Surgery, Trinity St. James’s Cancer Institute, Trinity Translational Medicine Institute, Trinity College Dublin, St. James’s HospitalAbstract Integration of multi-omic data for the purposes of biomarker discovery can provide novel and robust panels across multiple biological compartments. Appropriate analytical methods are key to ensuring accurate and meaningful outputs in the multi-omic setting. Here, we extensively profile the proteome and transcriptome of patient pancreatic cyst fluid (PCF) (n = 32) and serum (n = 68), before integrating matched omic and biofluid data, to identify biomarkers of pancreatic cancer risk. Differential expression analysis, feature reduction, multi-omic data integration, unsupervised hierarchical clustering, principal component analysis, spearman correlations and leave-one-out cross-validation were performed using RStudio and CombiROC software. An 11-feature multi-omic panel in PCF [PIGR, S100A8, REG1A, LGALS3, TCN1, LCN2, PRSS8, MUC6, SNORA66, miR-216a-5p, miR-216b-5p] generated an AUC = 0.806. A 13-feature multi-omic panel in serum [SHROOM3, IGHV3-72, IGJ, IGHA1, PPBP, APOD, SFN, IGHG1, miR-197-5p, miR-6741-5p, miR-3180, miR-3180-3p, miR-6782-5p] produced an AUC = 0.824. Integration of the strongest performing biomarkers generated a 10-feature cross-biofluid multi-omic panel [S100A8, LGALS3, SNORA66, miR-216b-5p, IGHV3-72, IGJ, IGHA1, PPBP, miR-3180, miR-3180-3p] with an AUC = 0.970. Multi-omic profiling provides an abundance of potential biomarkers. Integration of data from different omic compartments, and across biofluids, produced a biomarker panel that performs with high accuracy, showing promise for the risk stratification of patients with pancreatic cystic lesions.https://doi.org/10.1038/s41598-024-83742-4Pancreatic cancerPancreatic cystic lesionRisk stratificationBiomarkerMulti-omics
spellingShingle Laura E. Kane
Gregory S. Mellotte
Eimear Mylod
Paul Dowling
Simone Marcone
Caitriona Scaife
Elaine M. Kenny
Michael Henry
Paula Meleady
Paul F. Ridgway
Finbar MacCarthy
Kevin C. Conlon
Barbara M. Ryan
Stephen G. Maher
Multi-omic biomarker panel in pancreatic cyst fluid and serum predicts patients at a high risk of pancreatic cancer development
Scientific Reports
Pancreatic cancer
Pancreatic cystic lesion
Risk stratification
Biomarker
Multi-omics
title Multi-omic biomarker panel in pancreatic cyst fluid and serum predicts patients at a high risk of pancreatic cancer development
title_full Multi-omic biomarker panel in pancreatic cyst fluid and serum predicts patients at a high risk of pancreatic cancer development
title_fullStr Multi-omic biomarker panel in pancreatic cyst fluid and serum predicts patients at a high risk of pancreatic cancer development
title_full_unstemmed Multi-omic biomarker panel in pancreatic cyst fluid and serum predicts patients at a high risk of pancreatic cancer development
title_short Multi-omic biomarker panel in pancreatic cyst fluid and serum predicts patients at a high risk of pancreatic cancer development
title_sort multi omic biomarker panel in pancreatic cyst fluid and serum predicts patients at a high risk of pancreatic cancer development
topic Pancreatic cancer
Pancreatic cystic lesion
Risk stratification
Biomarker
Multi-omics
url https://doi.org/10.1038/s41598-024-83742-4
work_keys_str_mv AT lauraekane multiomicbiomarkerpanelinpancreaticcystfluidandserumpredictspatientsatahighriskofpancreaticcancerdevelopment
AT gregorysmellotte multiomicbiomarkerpanelinpancreaticcystfluidandserumpredictspatientsatahighriskofpancreaticcancerdevelopment
AT eimearmylod multiomicbiomarkerpanelinpancreaticcystfluidandserumpredictspatientsatahighriskofpancreaticcancerdevelopment
AT pauldowling multiomicbiomarkerpanelinpancreaticcystfluidandserumpredictspatientsatahighriskofpancreaticcancerdevelopment
AT simonemarcone multiomicbiomarkerpanelinpancreaticcystfluidandserumpredictspatientsatahighriskofpancreaticcancerdevelopment
AT caitrionascaife multiomicbiomarkerpanelinpancreaticcystfluidandserumpredictspatientsatahighriskofpancreaticcancerdevelopment
AT elainemkenny multiomicbiomarkerpanelinpancreaticcystfluidandserumpredictspatientsatahighriskofpancreaticcancerdevelopment
AT michaelhenry multiomicbiomarkerpanelinpancreaticcystfluidandserumpredictspatientsatahighriskofpancreaticcancerdevelopment
AT paulameleady multiomicbiomarkerpanelinpancreaticcystfluidandserumpredictspatientsatahighriskofpancreaticcancerdevelopment
AT paulfridgway multiomicbiomarkerpanelinpancreaticcystfluidandserumpredictspatientsatahighriskofpancreaticcancerdevelopment
AT finbarmaccarthy multiomicbiomarkerpanelinpancreaticcystfluidandserumpredictspatientsatahighriskofpancreaticcancerdevelopment
AT kevincconlon multiomicbiomarkerpanelinpancreaticcystfluidandserumpredictspatientsatahighriskofpancreaticcancerdevelopment
AT barbaramryan multiomicbiomarkerpanelinpancreaticcystfluidandserumpredictspatientsatahighriskofpancreaticcancerdevelopment
AT stephengmaher multiomicbiomarkerpanelinpancreaticcystfluidandserumpredictspatientsatahighriskofpancreaticcancerdevelopment