Elevated Serum Matrix Metalloproteinase-3 and -7 in H. pylori-Related Gastric Cancer Can Be Biomarkers Correlating with a Poor Survival

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Abstract
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. 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. 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). 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.

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