Elevated serum matrix metalloproteinase-3 and -7 in H. pylori-related gastric cancer can be biomarkers correlating with a poor survival

Dig Dis Sci. 2010 Jun;55(6):1649-57. doi: 10.1007/s10620-009-0926-x. Epub 2009 Aug 19.

Abstract

Background: Helicobacter pylori (H. pylori) infection up-regulates the expression of matrix metalloproteinases (MMPs), which may be involved in chronic inflammation, ulceration, and even cancer development. This study aimed to test if serum levels of MMP-3, -7, and -9 are correlated with different clinical outcomes in H. pylori-infected subjects and if these are predictive of progression to H. pylori-related gastric cancer.

Method: Two hundred one patients, 28 with H. pylori-negative gastritis and 173 with different H. pylori-positive gastrointestinal diseases (46 gastritis, 43 duodenal ulcers, 29 gastric ulcers, and 55 gastric cancers) were assessed for serum MMP-3, -7, and -9 titers by enzyme-linked immunosorbent assay and validated to their correlations with the different clinical features and survival of patients with H. pylori-positive gastric cancer.

Results: Among the H. pylori-infected subjects, gastric cancer patients had higher serum levels of MMP-3 and MMP-7 than those with duodenal ulcer and gastritis (P < 0.05). For gastric cancer patients, concomitant elevated MMP-3 (>14 ng/ml) and MMP-7 (>4.5 ng/ml) independently correlated with lymph node invasion (P < 0.05) and could be predictive to have shorter 2- or 5-year survivals (log rank test, P = 0.006).

Conclusion: Concomitant elevations of MMP-3 and MMP-7 serum levels in the H. pylori-infected gastric cancer patients could serve as potential biomarkers to correlate with poor survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers, Tumor / blood*
  • Case-Control Studies
  • Chi-Square Distribution
  • Disease Progression
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Helicobacter Infections / complications
  • Helicobacter Infections / enzymology*
  • Helicobacter Infections / microbiology
  • Helicobacter pylori / pathogenicity*
  • Humans
  • Kaplan-Meier Estimate
  • Logistic Models
  • Lymphatic Metastasis
  • Male
  • Matrix Metalloproteinase 3 / blood*
  • Matrix Metalloproteinase 7 / blood*
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Proportional Hazards Models
  • Risk Assessment
  • Risk Factors
  • Stomach Neoplasms / enzymology*
  • Stomach Neoplasms / microbiology
  • Stomach Neoplasms / mortality*
  • Stomach Neoplasms / secondary
  • Time Factors
  • Up-Regulation

Substances

  • Biomarkers, Tumor
  • MMP3 protein, human
  • Matrix Metalloproteinase 3
  • MMP7 protein, human
  • Matrix Metalloproteinase 7