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

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.

Mucins as Potential Biomarkers for Early Detection of Cancer

“…However, these reports suggest that MUC5AC, in combination with CA19-9, is a reliable biomarker for the early detection of PC. Other mucins, such as MUC1 and MUC16, were also evaluated in combination with CA19-9 for PDAC diagnosis [ 232 , 233 , 234 ]. Interestingly, both MUC1 and MUC16 were found to complement the diagnostic efficacy of CA19-9.…”

Advanced iron oxide nanotheranostics for multimodal and precision treatment of pancreatic ductal adenocarcinoma

“…Nanoparticle/drug delivery into CD44 overexpressing tumor cells offers the chance to overcome drug resistance in cancer stem-like cells (Li et al, 2015). Hyaluronic acid References for biomarker serum concentration: uPAR (Loosen et al, 2019); EGFR and HER2 (Brand et al, 2011), CD44 (Gansauge et al, 1997), mesothelin (Kendrick et al, 2014), MUC1 (Gold et al, 2006), Folate receptor α, MUC16 and CEA (Song et al, 2021), and Epcam (Gebauer et al, 2014).…”

“…The levels of biomarker concentrations in the blood of healthy human were detected by Mass spectrometry. The levels of biomarker proteins in the blood of pancreatic cancer patients were determined by immunological assay, such as ELISA. References for biomarker serum concentration: uPAR (Loosen et al, 2019); EGFR and HER2 (Brand et al, 2011), CD44 (Gansauge et al, 1997), mesothelin (Kendrick et al, 2014), MUC1 (Gold et al, 2006), Folate receptor α, MUC16 and CEA (Song et al, 2021), and Epcam (Gebauer et al, 2014).…”

“…References for biomarker serum concentration: uPAR (Loosen et al, 2019); EGFR and HER2 (Brand et al, 2011), CD44 (Gansauge et al, 1997), mesothelin (Kendrick et al, 2014), MUC1 (Gold et al, 2006), Folate receptor α, MUC16 and CEA (Song et al, 2021), and Epcam (Gebauer et al, 2014).…”

“…As shown in Table 1, in the blood of the healthy human subjects, relatively high basal levels plasma concentrations of CD44, HER‐2, EGFR, and folate receptor α are found by the mass spectrometry analysis. PDAC patients have increased plasma levels of MUC1, MUC16, or mesothelin (Kendrick et al, 2014; Song et al, 2021). Currently, the impact of a high plasma level of target receptors on the efficiency of intratumoral delivery of the corresponding targeted nanoparticle/drug has yet to be investigated.…”