Blood-Based microRNA Biomarker Signature of Early-Stage Pancreatic Ductal Adenocarcinoma With Lead-Time Trajectory in Prediagnostic Samples

Authors

Warapen Treekitkarnmongkol
Jianliang Dai
Suyu Liu
Deivendran Sankaran
Tristian Nguyen
Seetharaman Balasenthil
Mark W Hurd
Meng Chen
Hiroshi Katayama
Sinchita Roy-Chowdhuri
George A Calin
Randall E Brand
Paul D Lampe
Tony Y Hu
Anirban Maitra
Eugene J Koay
Ann M Killary
Subrata Sen

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