Validation of Serum Biomarkers That Complement CA19-9 in Detecting Early Pancreatic Cancer Using Electrochemiluminescent-Based Multiplex Immunoassays.

Jin Song,Lori J Sokoll,Daniel W Chan,Zhen Zhang

doi:10.3390/biomedicines9121897

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy; its early detection is critical for improving prognosis. Electrochemiluminescent-based multiplex immunoassays were developed with high analytical performance. All proteins were analyzed in sera of patients diagnosed with PDAC (n = 138), benign pancreatic conditions (111), and healthy controls (70). The clinical performance of these markers was evaluated individually or in combination for their complementarity to CA19-9 in detecting early PDAC. Logistic regression modeling including sex and age as cofactors identified a two-marker panel of CA19-9 and CA-125 that significantly improved the performance of CA19-9 alone in discriminating PDAC (AUC: 0.857 vs. 0.766), as well as early stage PDAC (0.805 vs. 0.702) from intraductal papillary mucinous neoplasm (IPMN). At a fixed specificity of 80%, the panel significantly improved sensitivities (78% vs. 41% or 72% vs. 59%). A two-marker panel of HE4 and CEA significantly outperformed CA19-9 in separating IPMN from chronic pancreatitis (0.841 vs. 0.501). The biomarker panels evaluated by assays demonstrated potential complementarity to CA19-9 in detecting early PDAC, warranting additional clinical validation to determine their role in the early detection of pancreatic cancer.

Highlights

Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignant tumor with high metastatic potential
A total of 319 archived serum samples obtained from 138 patients with histologically diagnosed PDAC, 111 patients with benign pancreatic conditions, including both intraductal papillary mucinous neoplasms (IPMN) and chronic pancreatitis (CP), and 70 healthy controls without a history of pancreatic diseases were studied with institutional approval
It should be noted that nonspecific cross-reactivity was observed at recombinant protein concentrations that exceeded physiological levels, thereby reducing the chance of cross-reactivity in physiological human serum samples

Summary

Introduction

Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignant tumor with high metastatic potential. The current gold-standard serum marker CA19-9 is used in the clinic only for disease monitoring, because it lacks the necessary sensitivity and specificity due to its absence in 5–10% of patients with a Lewis-negative genotype and because it is frequently elevated in non-malignant conditions, such as pancreatitis and other benign conditions [4,5,6]. All of these factors limit its clinical utility in a screening and early detection setting. There is an urgent clinical need to identify additional biomarkers to complement CA19-9 for the early detection of PDAC

Methods

Results

Conclusion