Titre
Differences in the gene expression profile of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) in primary colorectal tumors and their synchronous liver metastases.
Type
article
Institution
Externe
Périodique
Auteur(s)
Gentner, B.
Auteure/Auteur
Wein, A.
Auteure/Auteur
Croner, R.S.
Auteure/Auteur
Zeittraeger, I.
Auteure/Auteur
Wirtz, R.M.
Auteure/Auteur
Roedel, F.
Auteure/Auteur
Dimmler, A.
Auteure/Auteur
Dorlaque, L.
Auteure/Auteur
Hohenberger, W.
Auteure/Auteur
Hahn, E.G.
Auteure/Auteur
Brueckl, W.M.
Auteure/Auteur
Liens vers les personnes
ISSN
0250-7005
Statut éditorial
Publié
Date de publication
2009-01
Volume
29
Numéro
1
Première page
67
Dernière page/numéro d’article
74
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Résumé
Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) have been strongly implicated in the pathogenesis of many types of human cancer. We wanted to specifically define their role in established colorectal cancer liver metastases.
The MMP/TIMP expression profiles of N=9 colorectal primary tumour liver metastasis tissue pairs were determined using oligonucleotide-based arrays. Expression levels for the most relevant MMPs were confirmed by reverse-transcriptase polymerase chain reaction (RT-PCR). Additionally, unsupervised clustering using the MMP/TIMP profile of N=25 colorectal cancer liver metastases was performed and the response to palliative 5-fluorouracil (5-FU)-based chemotherapy was assessed using radiological response criteria.
When comparing the primary tumors to their synchronous liver metastases, a statistically significant (p < 0.05) down-regulation of MMP1, -2, -3 and -12 was found in the metastases. Unsupervised clustering using the MMP/TIMP profiles of 25 liver metastases revealed two distinct subgroups with different responses to palliative, 5-FU-based chemotherapy (response rates: 22% vs. 56%, respectively). In particular, higher MMP7, TIMP1 and TIMP2 levels were found in the unfavourable group, while higher expression of MMP2, -9, -11 and -14 was associated with a more favourable response to chemotherapy.
Colorectal cancer liver metastases show a distinctive MMP/TIMP profile with predictive implications.
The MMP/TIMP expression profiles of N=9 colorectal primary tumour liver metastasis tissue pairs were determined using oligonucleotide-based arrays. Expression levels for the most relevant MMPs were confirmed by reverse-transcriptase polymerase chain reaction (RT-PCR). Additionally, unsupervised clustering using the MMP/TIMP profile of N=25 colorectal cancer liver metastases was performed and the response to palliative 5-fluorouracil (5-FU)-based chemotherapy was assessed using radiological response criteria.
When comparing the primary tumors to their synchronous liver metastases, a statistically significant (p < 0.05) down-regulation of MMP1, -2, -3 and -12 was found in the metastases. Unsupervised clustering using the MMP/TIMP profiles of 25 liver metastases revealed two distinct subgroups with different responses to palliative, 5-FU-based chemotherapy (response rates: 22% vs. 56%, respectively). In particular, higher MMP7, TIMP1 and TIMP2 levels were found in the unfavourable group, while higher expression of MMP2, -9, -11 and -14 was associated with a more favourable response to chemotherapy.
Colorectal cancer liver metastases show a distinctive MMP/TIMP profile with predictive implications.
Sujets
PID Serval
serval:BIB_E49FB20975C1
PMID
Date de création
2022-07-13T15:13:36.688Z
Date de création dans IRIS
2025-05-21T06:07:30Z