Prognostic Values of Matrix Metalloproteinase Family Expression in Human Colorectal Carcinoma

Background

We examined expression patterns of matrix metalloproteinase (MMP), tissue inhibitor of metalloproteinase (TIMP), and reversion-inducing cysteine-rich protein with Kazal motifs (RECK) in colorectal cancer tissues to assess their prognostic significance.

Materials and methods

mRNA expressions of 17 MMPs, 4 TIMPs, and RECK were measured in 112 colorectal cancerous tissues, 20 normal mucosa tissues, and 11 metastatic liver lesions by real-time reverse-transcriptional-polymerase chain reaction. The protein level expressions were confirmed with immunohistochemistry.

Results

Cancers and normal mucosa displayed highly significant differences (P < 0.01) in expression of nine genes (MMP-1, -3, -7, -9, -10, -11, -12, -14, and RECK). Primary cancers and metastatic lesions showed highly significant differences (P < 0.01) in MMP-1, -10, -11, and TIMP-1. MMP-12 expression was higher in the primary tumors that were associated without hepatic metastasis than those with metastasis (P < 0.01). High expression of MMP-15 was related to longer disease-free survival (generalized Wilcoxon test, P < 0.0062; Cox hazard model, P < 0.028, hazard ratio, 0.099).

Conclusions

MMP, TIMP, RECK expression patterns may provide an insight into extracellular matrix degrading (which is characteristic of colorectal cancers) and its role in metastasis.

Key Words: matrix metalloproteinase (MMP)-15, colorectal cancer, hepatic metastasis, recurrence, prognosis