A Rigorous Multi-laboratory Study of Known Pdac Biomarkers Identifies Increased Sensitivity and Specificity Over CA19-9 Alone

Authors

Brian Haab
Lu Qian
Ben Staal
Maneesh Jain
Johannes Fahrmann
Christine Worthington
Denise Prosser
Liudmila Velokokhatnaya
Camden Lopez
Runlong Tang
Mark W Hurd
Gopalakrishnan Natarajan
Sushil Kumar
Lynette Smith
Sam Hanash
Surinder K Batra
Anirban Maitra
Anna Lokshin
Ying Huang
Randall E Brand

Publication Date

11-1-2024

Journal

Cancer Letters

Abstract

A blood test that enables surveillance for early-stage pancreatic ductal adenocarcinoma (PDAC) is an urgent need. Independent laboratories have reported PDAC biomarkers that could improve biomarker performance over CA19-9 alone, but the performance of the previously reported biomarkers in combination is not known. Therefore, we conducted a coordinated case/control study across multiple laboratories using common sets of blinded training and validation samples (132 and 295 plasma samples, respectively) from PDAC patients and non-PDAC control subjects representing conditions under which surveillance occurs. We analyzed the training set to identify candidate biomarker combination panels using biomarkers across laboratories, and we applied the fixed panels to the validation set. The panels identified in the training set, CA19-9 with CA199.STRA, LRG1, TIMP-1, TGM2, THSP2, ANG, and MUC16.STRA, achieved consistent performance in the validation set. The panel of CA19-9 with the glycan biomarker CA199.STRA improved sensitivity from 0.44 with 0.98 specificity for CA19-9 alone to 0.71 with 0.98 specificity (p < 0.001, 1000-fold bootstrap). Similarly, CA19-9 combined with the protein biomarker LRG1 and CA199.STRA improved specificity from 0.16 with 0.94 sensitivity for CA19-9 to 0.65 with 0.89 sensitivity (p < 0.001, 1000-fold bootstrap). We further validated significantly improved performance using biomarker panels that did not include CA19-9. This study establishes the effectiveness of a coordinated study of previously discovered biomarkers and identified panels of those biomarkers that significantly increased the sensitivity and specificity of early-stage PDAC detection in a rigorous validation trial.

Keywords

Humans, Biomarkers, Tumor, Carcinoma, Pancreatic Ductal, Pancreatic Neoplasms, Case-Control Studies, Female, Male, CA-19-9 Antigen, Middle Aged, Sensitivity and Specificity, Aged, Antigens, Tumor-Associated, Carbohydrate, Pancreatic adenocarcinoma, early detection, biomarkers, CA 19-9, panel

DOI

10.1016/j.canlet.2024.217245

PMID

39276915

PMCID

PMC11808537

PubMedCentral® Posted Date

2-10-2025

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes