Serum tissue inhibitor of metalloproteinase 1 (TIMP-1) and vascular endothelial growth factor A (VEGF-A) are associated with prognosis in esophageal cancer patients

Adv Med Sci. 2013;58(2):227-34. doi: 10.2478/ams-2013-0017.

Abstract

Purpose: The matrix metalloproteinases, tissue inhibitors of metalloproteinases and angiogenesis contribute to growth and spread of cancer. We investigated the correlation between pretreatment serum levels of tissue inhibitor of metalloproteinase 1 (TIMP-1) and vascular endothelial growth factor A (VEGF-A), and clinicopathologic features and survival in patients with esophageal cancer (EC).

Material/methods: Serum TIMP-1 and VEGF-A were measured by enzyme-linked immunosorbent assay (ELISA) in 89 patients with EC, and 30 healthy controls.

Results: Serum TIMP-1 and VEGF-A levels were significantly higher in patients with esophageal carcinoma than in the control group (p=0.001 and p<0.001, respectively). High levels of TIMP-1 were associated with histological type (p<0.001), tumor depth (p<0.001), stage (p<0.001) and lymph node metastases (p=0.001). Subgroup analysis showed that tumor size (p<0.001), tumor depth (p<0.001), stage (p<0.001), lymph node metastases (p=0.002), distant metastases (p=0.009) and resectability (p=0.003), were correlated with an elevated level of VEGF-A. Patients with elevated levels of TIMP-1 and VEGF-A had a significantly lower overall survival (p=0.02 and p=0.048, respectively), and disease-free survival (TIMP-1, p<0.001).

Conclusion: High serum levels of TIMP-1 and VEGF-A were found to be associated with tumor progression and unfavorable prognosis in patients with EC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / mortality
  • Adenocarcinoma / secondary
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / blood
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / secondary
  • Disease-Free Survival
  • Enzyme-Linked Immunosorbent Assay
  • Esophageal Neoplasms / metabolism*
  • Esophageal Neoplasms / mortality
  • Esophageal Neoplasms / pathology
  • Female
  • Follow-Up Studies
  • Humans
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Tissue Inhibitor of Metalloproteinase-1 / blood*
  • Vascular Endothelial Growth Factor A / blood*

Substances

  • Biomarkers, Tumor
  • TIMP1 protein, human
  • Tissue Inhibitor of Metalloproteinase-1
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A