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.


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.
Asano
Toshimichi
T
Division of Cancer-Related Genes, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan.
Tada
Mitsuhiro
M
Cheng
Shaoqiang
S
Takemoto
Norihiro
N
Kuramae
Taro
T
Abe
Motoki
M
Takahashi
Osamu
O
Miyamoto
Masaki
M
Hamada
Jun-Ichi
J
Moriuchi
Tetsuya
T
Kondo
Satoshi
S
D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D058851:GPI-Linked Proteins; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000556:secondary; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D053506:Matrix Metalloproteinase 10 / Q000378:metabolism; D053507:Matrix Metalloproteinase 11 / Q000378:metabolism; D053517:Matrix Metalloproteinase 15 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000378:metabolism; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism
D058851:GPI-Linked Proteins; D008562:Membrane Glycoproteins; C115460:RECK protein, human; D012333:RNA, Messenger; D019714:Tissue Inhibitor of Metalloproteinases; D053507:Matrix Metalloproteinase 11; D053517:Matrix Metalloproteinase 15; D020782:Matrix Metalloproteinases; D053506:Matrix Metalloproteinase 10; D020781:Matrix Metalloproteinase 1