Clinical Value of Circulating Lipocalins and Insulin-Like Growth Factor Axis in Pancreatic Cancer Diagnosis

Abstract

Early diagnosis of pancreatic cancer (PC) in diabetic patients is difficult owing to late presentation of symptoms. Hence, finding a marker to identify cancer stage early would be useful to improve survival. We aimed to determine levels of serum retinol binding protein 4 (RBP-4), neutrophil gelatinase-associated lipocalin (NGAL), insulin-like growth factor I (IGF-I), and its binding protein 3 (IGFBP-3) in patients with PC with preexisting type 2 diabetes. Moreover, we assessed their clinical usefulness in PC diagnosis and their association with tumor severity. Twenty-three patients with PC, 32 diabetic patients, and 20 healthy controls were examined. Preoperative and postoperative samples were obtained from 15 patients with PC. Serum insulin, cancer antigen (CA 19-9), RBP-4, NGAL, IGF-I, and IGFBP-3 levels were estimated by enzyme-linked immunosorbent assay. Significant elevation in the levels of RBP-4 (60.1 [46.3-71.4] ng/mL), NGAL (142 [80-235] ng/mL), and IGF-I (174 [9.3] ng/mL) together with significant reduction in the level of IGFBP-3 (3669 [299] ng/mL) was found in patients with PC. Moreover, RBP-4 and NGAL levels were reduced in postoperative samples compared with preoperative ones. Receiver operating characteristic curve analysis revealed that they can distinguish PC from non-PC cases with significant area under the curve. Retinol binding protein 4, NGAL, IGF-I, and IGFBP-3 are associated with PC in type 2 diabetic patients. They could be useful in distinguishing PC from non-PC cases when used in combination or with cancer antigen.