Neutrophil gelatinase-associated lipocalin, macrophage inhibitory cytokine 1, and carbohydrate antigen 19-9 in pancreatic juice: pathobiologic implications in diagnosing benign and malignant disease of the pancreas

Abstract

Objective: Pancreatic diseases pose significant diagnostic challenge as signs and symptoms often overlap. We investigated the potential of pancreatic juice neutrophil gelatinase-associated lipocalin, macrophage inhibitory cytokine 1 (MIC-1), and carbohydrate antigen 19-9 (CA19-9) to aid in the diagnosis of patients with symptoms suggestive of pancreatic diseases.

Methods: A total of 105 chronic pancreatitis (CP), pancreatic cancer (PC), and nonpancreatic nonhealthy (patients with symptoms mimicking pancreatic disease but found to be free of any pancreatic disease) patients underwent endoscopic pancreatic juice collection after secretin stimulation. Neutrophil gelatinase-associated lipocalin and MIC-1 levels were measured by enzyme-linked immunosorbent assay, whereas CA19-9 was measured by radioimmunoassay.

Results: Neutrophil gelatinase-associated lipocalin, MIC-1, and CA19-9 were significantly elevated in the pancreatic juice of patients with CP and patients with PC as compared with nonpancreatic nonhealthy controls (P ≤ 0.034). Neutrophil gelatinase-associated lipocalin seemed most promising in differentiating diseased versus nondiseased pancreata (areas under the curve, 0.88-0.91), whereas MIC-1 was found to be higher in patients with PC than in patients with CP (P = 0.043). Interestingly, MIC-1 levels in diabetic patients with PC were higher than in nondiabetic patients with PC (P = 0.030) and diabetic patients with CP (P = 0.087). Carbohydrate antigen 19-9 showed the least ability to distinguish patient groups (areas under the curve, 0.61-0.76).

Conclusions: Pancreatic juice neutrophil gelatinase-associated lipocalin shows potential utility in establishing pancreatic etiology in the context of nonspecific symptoms, whereas MIC-1 may aid in differentiating PC from CP.

Conflict of interest statement

Disclosures: The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Figures

Figure 1. Distribution of biomarkers analyzed in the pancreatic juice of non-pancreatic non-healthy, chronic pancreatitis, and pancreatic cancer patients

Distribution of pancreatic juice macrophage inhibitor cytokine-1 (MIC-1; A); neutrophil gelatinase–associated lipocalin (NGAL; B); and carbohydrate antigen 19-9 (CA19-9; C) of non-pancreatic non-healthy (NPNH) patients, chronic pancreatitis (CP) patients, and pancreatic cancer (PC) patients. NGAL and MIC-1 were measured by enzyme-linked immunosorbent assay (ELISA), while CA19-9 was measured by radioimmunoassay. MIC-1 and NGAL values are given in ng/mL, CA19-9 values are given in U/mL.

Figure 2. Comparison ROC curves examining the ability of tested biomarkers to discriminate between chronic pancreatitis, pancreatic cancer, and non-pancreatic non-healthy patients

Receiver-operating characteristic curves examining the ability of macrophage inhibitor cytokine-1 (MIC-1); neutrophil gelatinase–associated lipocalin (NGAL); and carbohydrate antigen 19-9 (CA19-9) to differentiate A) non-pancreatic non-healthy (NPNH) patients from pancreatic cancer (PC) patients; B) chronic pancreatitis (CP) patients from PC patients; and C) CP patients from NPNH patients. Both NGAL and MIC-1 were found to be superior to CA19-9 in differentiating patients with pancreatic disease (PC and CP) from their NPNH counterparts.