
Faculty, Staff and Student Publications
Publication Date
1-1-2024
Journal
Gastro Hep Advances
Abstract
Background and aims: Clinically validated biomarker of pancreatic ductal adenocarcinoma (PDAC), carbohydrate antigen 19-9 (CA19-9), has limited sensitivity and specificity for early-stage disease. Circulating miRNAs in plasma associated with cancer relevant pathways were developed as early detection biomarkers.
Methods: 2083 miRNAs in 15 μl of plasma from multicenter age-matched cohorts (N = 203: healthy controls, n = 46; pancreatitis controls, n = 36; diagnosed cases: n = 121) and a prediagnostic Prostate, Lung, Colorectal, and Ovarian age- and gender-matched cohort (N = 96; controls, n = 48; prediagnosed cases, n = 48) were interrogated. A three-miRNA biomarker signature was developed for early-stage PDAC.
Results: The three-miRNA signature (let-7i-5p, miR-130a-3p and miR-221-3p) detected PDAC from healthy controls independently (area under the curve [AUC] of stage I, II, I-IV = 0.970, 0.975, 0.974) and in combination with CA19-9 (AUC of stage I, II, I-IV = 1.000, 0.992, 0.995). It also discriminated chronic pancreatitis (AUC of stage I, II, I-IV = 0.932, 0.931, 0.929), improving performance of CA19-9 alone (AUC of stage I, II, I-IV = 0.763, 0.701, 0.735) in combination (AUC of stage I, II, I-IV = 0.971, 0.943, 0.951). Blinded validation in prediagnostic Prostate, Lung, Colorectal, and Ovarian cohort revealed lead-time trajectory increase in AUC from 0.702 to 0.729 to 0.757 at twelve-, six-, and three-months before PDAC diagnosis, respectively. The signature also helped stratification of patients with different circulating tumor DNA and imaging subtypes.
Conclusion: Plasma miRNAs associated with oncogenic pathways may serve as PDAC early detection biomarkers.
Keywords
Early Detection Biomarkers, Liquid Biopsy, Pancreatic Ductal Adenocarcinoma, Plasma miRNA, Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial
DOI
10.1016/j.gastha.2024.08.002
PMID
39529638
PMCID
PMC11550741
PubMedCentral® Posted Date
8-6-2024
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
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Bioinformatics Commons, Biomedical Informatics Commons, Genetic Phenomena Commons, Medical Genetics Commons, Oncology Commons