Abstract
Introduction
The accurate identification of mucinous pancreatic cystic lesions (PCLs) is paramount
for cancer risk stratification. Cyst fluid carcinoembryonic antigen (CEA), the only
routinely used test, requires high volumes and has low sensitivity. We aimed to compare
the performance of two investigational small-volume biomarkers, glucose and the protease
gastricsin, to CEA for PCL classification.
Methods
We obtained cyst fluid samples from 81 patients with pathologically confirmed PCLs
from four institutions between 2003 and 2016. Gastricsin activity was measured using
an internally quenched fluorescent substrate. Glucose levels were measured with a
standard glucometer. CEA levels were obtained from the medical record. Models using
Classification and Regression Trees were created to predict mucinous status. Model
performance was evaluated using nested cross-validation.
Results
Gastricsin activity, CEA, and glucose levels from patients with mucinous (n = 50) and nonmucinous (n = 31) PCLs were analyzed. Area under the curve (AUC) was similar for individual classifiers
(gastricsin volume normalized [GVN] 0.88; gastricsin protein concentration normalized
[GPN] 0.95; glucose 0.83; CEA 0.84). The combination of two classifiers did not significantly
improve AUC, with CEA + GVN (0.88) performing similarly to CEA + GPN (0.95), GVN + glucose
(0.87), GPN + glucose (0.95), and CEA + glucose (0.84). The three-analyte combination
performed similarly to single and dual classifiers (GPN + glucose + CEA AUC 0.95;
GVN + glucose + CEA AUC 0.87). After multiple comparison corrections, there were no
significant differences between the individual, dual, and triple classifiers.
Conclusions
Gastricsin and glucose performed similarly to CEA and required <5% of the volume required
for CEA; these classifiers may be useful in patients with limited cyst fluid. Future
multicenter prospective studies are needed to validate and compare these novel small-volume
biomarkers.
Keywords
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Article info
Publication history
Published online: November 08, 2022
Accepted:
August 19,
2022
Received in revised form:
July 26,
2022
Received:
December 29,
2021
Publication stage
In Press Corrected ProofIdentification
Copyright
© 2022 Published by Elsevier Inc.
