Serum IGFBP2 and MSLN as diagnostic and prognostic biomarkers for pancreatic cancer

Abstract

Background: Identification of diagnostic and prognostic biomarkers is a research priority for the improved management of pancreatic ductal adenocarcinoma (PDAC). Insulin-like growth factor binding protein 2 (IGFBP2) and mesothelin (MSLN) have shown potential as serum biomarkers in other cancers, but have not been adequately studied in PDAC.

Methods: Serum IGFBP2 and MSLN levels were quantified by enzyme-linked immunosorbent assay (ELISA) in a cohort of 84 PDAC patients, 84 healthy control subjects and 40 chronic pancreatitis (ChPT) patients. Regression models related IGFBP2 and MSLN levels to diagnosis, gender, age, stage and survival.

Results: IGFPB2 and MSLN serum levels were diagnostic for PDAC in age-adjusted models (P = 0.032 and P = 0.002, respectively) when compared with ChPT and healthy control samples. At a 95% specificity threshold, the sensitivity for IGFBP2 was 22% and the sensitivity for MSLN was 17%. Neither protein approached the diagnostic accuracy of CA 19-9. However, IGFBP2 or MSLN or both correctly identified 18 of the 28 samples misidentified by CA 19-9. In age-adjusted models, neither serum IGFBP2 (P = 0.36) nor MSLN (P = 0.29) were significant predictors of survival.

Discussion: Serum IGFBP2 and MSLN are weak diagnostic classifiers individually, but may be useful in a diagnostic biomarker panel.

Figure 1

Mean serum protein levels of insulin-like growth factor binding protein 2 (IGFBP2) and mesothelin (MSLN). IGFBP2 (a) and MSLN (b) were measured in serum samples obtained from healthy control subjects (CON), patients with chronic pancreatitis (ChPT) and pre-treatment patients with confirmed pancreatic ductal adenocarcinoma (PDAC). Error bars represent a standard deviation. *P = 0.069 versus CON, P = 0.0002 versus ChPT and P = 0.0022 versus CON + ChPT. †P = 0.0003 versus CON, P = 0.042 versus ChPT and P = 0.0002 versus CON + ChPT

Figure 2

Distribution of serum insulin-like growth factor binding protein 2 (IGFBP2) and mesothelin (MSLN) in individual samples. Each data point represents the serum level for IGFBP2 (a) and MSLN (B) in individual healthy control subjects (CON), patients with chronic pancreatitis (ChPT) and patients with pancreatic ductal adenocarcinoma (PDAC). A threshold value corresponding to a specificity of 95% is represented by a green line

Figure 3

Receiver-operating characteristics (ROC) curves for IGFBP2 (a), MSLN (b) and CA 19-9 (c). Dotted lines indicate the upper and lower 95% confidence levels. AUC = area under the curve

Figure 4

Stage distribution of serum insulin-like growth factor binding protein 2 (IGFBP2) and mesothelin (MSLN) in pancreatic ductal adenocarcinoma (PDAC) samples. Mean levels of IGFBP2 (a) and MSLN (b) at each stage are represented by the solid bars. Error bars indicate a standard deviation. *P < 0.03 versus all other stages by ANOVA and Tukey–Kramer post-hoc test