Clinical value of circulating lipocalins and insulin-like growth factor axis in pancreatic cancer diagnosis

Pancreas. 2013 Jan;42(1):149-54. doi: 10.1097/MPA.0b013e3182550d9d.

Abstract

Objectives: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

MeSH terms

  • Acute-Phase Proteins
  • Area Under Curve
  • Biomarkers / blood
  • CA-19-9 Antigen / blood
  • Case-Control Studies
  • Diabetes Mellitus, Type 2 / blood
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Insulin / blood
  • Insulin Resistance
  • Insulin-Like Growth Factor Binding Protein 3 / blood
  • Insulin-Like Growth Factor I / analysis*
  • Lipocalin-2
  • Lipocalins / blood*
  • Male
  • Middle Aged
  • Pancreatic Neoplasms / blood
  • Pancreatic Neoplasms / diagnosis*
  • Pancreatic Neoplasms / surgery
  • Predictive Value of Tests
  • Prognosis
  • Proto-Oncogene Proteins / blood*
  • ROC Curve
  • Retinol-Binding Proteins, Plasma / analysis
  • Signal Transduction*
  • Up-Regulation

Substances

  • Acute-Phase Proteins
  • Biomarkers
  • CA-19-9 Antigen
  • IGFBP3 protein, human
  • Insulin
  • Insulin-Like Growth Factor Binding Protein 3
  • LCN2 protein, human
  • Lipocalin-2
  • Lipocalins
  • Proto-Oncogene Proteins
  • RBP4 protein, human
  • Retinol-Binding Proteins, Plasma
  • Insulin-Like Growth Factor I