Serum dickkopf-1 is a novel serological biomarker for the diagnosis and prognosis of pancreatic cancer

Oncotarget. 2015 Aug 14;6(23):19907-17. doi: 10.18632/oncotarget.4529.

Abstract

Purpose: To identify whether Dickkopf-1 (DKK1) could be a potential biomarker for early detection and prognosis in patients with pancreatic cancer (PC).

Methods: Serum was collected from 140 patients with pancreatic adenocarcinoma and 92 control patients without pancreatic adenocarcinoma. Serological levels of DKK1 were examined by enzyme-linked immunosorbent assay (ELISA). The sensitivity and specificity was compared with carbohydrate antigen 19-9 (CA19-9). A 2-year follow-up was monitored to evaluate the correlation between DKK1 serum levels and overall survival. The expression of DKK1 in PC tumor tissues was also evaluated using immunohistochemistry staining.

Results: Serum levels of DKK1 and CA19-9 were elevated in PC patients in the early-stage cases. These levels increased with the advancement of clinical stage. There was significant difference in DKK1 serum levels between early and advanced PC stages. Receiver operating characteristic curve (ROCC) analysis showed that DKK1 was significantly better than CA19-9 in differentiating patients with PC from the controls (area under the curve (AUC) 0.919 versus 0.853, respectively), especially in distinguishing early-stage cancer from chronic pancreatitis (CP). The expression of DKK1 in PC tissues correlated with its expression in serum samples. The overall survival rate was 24.4% in the group with higher DKK1 levels and was found to be significantly different from the group with lower DKK1 levels (33.3%).

Conclusion: DKK1 may be a novel diagnostic/prognostic biomarker for PC.

Keywords: diagnosis; dickkopf-1 (DKK1); pancreatic cancer (PC); prognosis; serum biomarker.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Area Under Curve
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / blood*
  • CA-19-9 Antigen / blood
  • Carcinoma, Pancreatic Ductal / blood*
  • Carcinoma, Pancreatic Ductal / chemistry
  • Carcinoma, Pancreatic Ductal / mortality
  • Carcinoma, Pancreatic Ductal / pathology
  • Carcinoma, Pancreatic Ductal / therapy
  • Case-Control Studies
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Immunohistochemistry
  • Intercellular Signaling Peptides and Proteins / analysis
  • Intercellular Signaling Peptides and Proteins / blood*
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Pancreatic Neoplasms / blood*
  • Pancreatic Neoplasms / chemistry
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / pathology
  • Pancreatic Neoplasms / therapy
  • Predictive Value of Tests
  • ROC Curve
  • Risk Factors
  • Treatment Outcome

Substances

  • Biomarkers, Tumor
  • CA-19-9 Antigen
  • DKK1 protein, human
  • Intercellular Signaling Peptides and Proteins