Matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) in preoperative serum as independent prognostic markers in patients with colorectal cancer

Abstract

Colorectal cancer is one of the leading causes of cancer related death in developed countries. One of the reasons is the absence of tumor specific diagnostic and prognostic markers. The aim of this study was to examine the correlation of matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) expressions in serum and clinicopathological features of the colorectal adenocarcinoma. Another aim was to examine expression of MMP-9 in the tissue of the colorectal carcinoma in MMP-9 serum positive patients. In addition, we tried to establish the correlation between preoperative levels of serum markers (CEA and CA 19-9) and presence of MMP-2 or MMP-9. The study was performed on 32 patients with colorectal adenocarcinoma who underwent surgery and 11 patients in a control group who were operated for benign diseases. The samples were analyzed by SDS-PAGE to determine the molecular mass and SDS-PAGE zymography to determine levels of MMP-2 and MMP-9. Expression of MMP-9 was determined immunohistochemically in the tissue of the colorectal carcinoma of MMP-9 serum positive patients. MMP-2 and MMP-9 levels were increased in the serum of the patients with colorectal cancer compared to the control group. There was significant correlation in MMPs levels among the patients with tumor stage I and II and the patients with tumor stage III and IV. Obtained results did not demonstrate correlation between levels of CEA, CA 19-9 and presence of MMP-2 or MMP-9. MMP-9 expression was positive in 85% of MMP-9 serum positive patients with colorectal carcinoma. The overexpression of MMP-2 and MMP-9 strongly suggests its association with colorectal adenocarcinoma. Detection of MMP-2 and MMP-9 in serum might be useful for identification of patients with higher risk for colorectal cancer recurrence.

Silibinin inhibits the migration and invasion of human gastric cancer SGC7901 cells by downregulating MMP‑2 and MMP‑9 expression via the p38MAPK signaling pathway

“…Additionally, MMP-2 and MMP-9 were closely associated with lymph node metastasis, lymphatic invasion and prognosis of gastric cancer (32). Similar results have also been demonstrated in vitro, including gastric, ovarian and laryngeal cancer cells (33)(34)(35).…”

The Role of Matrix Metalloproteinases in Colorectal Cancer

“…One study found that MMP-2 and -9 protein levels were expressed at significantly higher ratios in the sera of persons with CRC compared to normal controls. This finding had greater diagnostic sensitivity than two other biomarkers currently used in clinical practice, CEA and CA19-9 [16]. In T3-T4 node-negative CRC, MMP-9 over-expression, CEA greater than 5 ng/mL and lymphatic invasion were associated with poor prognosis.…”

Serum matrix metalloproteinase 9 and colorectal neoplasia: a community-based evaluation of a potential diagnostic test

“…Serum levels have thus been shown to correlate significantly with plasma levels in two different diseases (Gerlach et al , 2009). Serum MMP9 levels have also been shown to be significantly associated with breast cancer stage and size (Motovali-Bashi et al , 2010), gastric cancer stage (Dragutinovic et al , 2009), stromal reaction in gastric cancer (Shen et al , 2000), and CRC stage (Dragutinovic et al , 2011). …”

“…Serum MMP9 levels have recently been shown to be significantly elevated in CRC patients compared with controls, and higher in late-stage colorectal neoplasia as compared with early-stage disease (Dragutinovic et al , 2011). Our pilot work suggested that serum MMP9 estimation is an acceptable test and has a high sensitivity and negative predictive value for colorectal neoplasia (Hurst et al , 2007).…”