Serum osteopontin and tissue inhibitor of metalloproteinase 1 as diagnostic and prognostic biomarkers for pancreatic adenocarcinoma

Pancreas. 2013 Mar;42(2):193-7. doi: 10.1097/MPA.0b013e31825e354d.

Abstract

Objectives: Pancreatic ductal adenocarcinoma (PDAC) has a dismal 5-year survival rate of 5%. There is an urgent need for early detection while the tumors are small and surgically resectable. We assessed serum osteopontin (OPN) and tissue inhibitor of metalloproteinase 1 (TIMP-1) as possible diagnostic and prognostic biomarkers in a novel cohort of patients with pancreatic cancer.

Methods: Osteopontin and TIMP-1 levels were determined in sera from 86 patients with PDAC, 86 healthy control subjects, and 48 patients with chronic pancreatitis. Regression models were used to relate OPN and TIMP-1 to sex, age, stage, class, and treatment. Survival analyses were performed using univariate and multivariate Cox models.

Results: The serum levels of both OPN and TIMP-1 distinguished PDAC from chronic pancreatitis (P ≤ 0.0001) and healthy control subjects (P < 0.0001). The serum levels of both OPN and TIMP-1 also distinguished early-stage resectable PDAC cases from chronic pancreatitis (P < 0.04) and healthy control subjects (P < 0.01). High serum levels of OPN were significantly correlated with reduced patient survival.

Conclusions: Serum OPN and TIMP-1 have use as diagnostic biomarkers in PDAC. Our data suggest a potential benefit of using OPN, TIMP-1, and CA 19-9 in a panel to improve diagnostic accuracy in PDAC.

Publication types

  • Comparative Study
  • Evaluation Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / blood*
  • CA-19-9 Antigen / blood
  • Carcinoma, Pancreatic Ductal / blood*
  • Carcinoma, Pancreatic Ductal / mortality
  • Carcinoma, Pancreatic Ductal / pathology
  • Carcinoma, Pancreatic Ductal / therapy
  • Case-Control Studies
  • Diagnosis, Differential
  • Early Detection of Cancer
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Linear Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Staging
  • Osteopontin / blood*
  • Pancreatic Neoplasms / blood*
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / pathology
  • Pancreatic Neoplasms / therapy
  • Pancreatitis, Chronic / blood
  • Predictive Value of Tests
  • Proportional Hazards Models
  • Time Factors
  • Tissue Inhibitor of Metalloproteinase-1 / blood*
  • Treatment Outcome
  • Up-Regulation

Substances

  • Biomarkers, Tumor
  • CA-19-9 Antigen
  • SPP1 protein, human
  • TIMP1 protein, human
  • Tissue Inhibitor of Metalloproteinase-1
  • Osteopontin