Overexpression of twist and matrix metalloproteinase-9 with metastasis and prognosis in gastric cancer

Asian Pac J Cancer Prev. 2013;14(9):5055-60. doi: 10.7314/apjcp.2013.14.9.5055.

Abstract

Objective: Twist, a basic helix-loop-helix transcription factor, plays a key role in the metastatic progression of human cancer. Matrix metalloproteinase (MMP)-9 is an endopeptidase that digests basement membrane type IV collagen, therefore being possibly related to tumor progression. It has been reported that Twist and matrix metalloproteinase-9 (MMP-9) are expressed in gastric cancers. However, the exact roles of Twist and MMP-9 in tumor metastasis and prognosis remain unclear. The aim of this study was to casts light on this question.

Methods: Twist and MMP-9 expression in tissue sections of 37 gastric carcinomas was evaluated with immunohistochemistry. The staining results were compared with clinicopathologic features and to patients'outcome.

Results: Twist positive expression was significantly increased in gastric cancer cases with lymph node metastasis (P=0.023). But no correlations were found between MMP-9 overexpression and clinicopathologic features, such as recurrence, TNM stage, and lymph node metastasis. Overall survival (OS) was significantly correlated with recurrence, serosa invasion, TNM stages, distant metastasis, and MMP-9 (P=0.027, 0.021, 0.000, 0.024 and 0.036, respectively). Disease-free survival (DFS) was prominently related to recurrence location, serosa invasion and TNM stages (P=0.000, 0.038 and 0.003, respectively). In the Cox regression multivariate analysis, TNM stage, distant metastasis and MMP-9 were significantly associated with prognosis of gastric cancer (P=0.002, 0.019, and 0.032, respectively).

Conclusions: This study showed Twist positive expression to be significantly correlated with lymph node metastasis in gastric cancer. MMP-9 overexpression is associated with OS, suggesting that MMP-9 is a prognostic indicator for survival in patients with gastric cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Carcinoma / diagnosis
  • Carcinoma / metabolism
  • Cohort Studies
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Lymph Nodes / pathology*
  • Lymphatic Metastasis
  • Male
  • Matrix Metalloproteinase 9 / metabolism*
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Nuclear Proteins / metabolism*
  • Prognosis
  • Proportional Hazards Models
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / pathology
  • Survival Rate
  • Twist-Related Protein 1 / metabolism*
  • Young Adult

Substances

  • Nuclear Proteins
  • TWIST1 protein, human
  • Twist-Related Protein 1
  • MMP9 protein, human
  • Matrix Metalloproteinase 9