Plasma Levels of Matrix Metalloproteinase-2 and Tissue Inhibitor of Metalloproteinase-1 Correlate With Disease Stage and Survival in Colorectal Cancer Patients

Waas, Erwin T.; Hendriks, T.; Lomme, Roger M. L. M.; Wobbes, Theo

doi:10.1007/s10350-004-0854-y

Cited by 68 publications

(69 citation statements)

References 33 publications

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“…On the contrary, the serum levels of MMP-2 and TIMP-2 in CRC patients were significantly lower than in healthy subjects. The obtained results are in line with the investigation of Waas et al, who showed that plasma pro-MMP-2 levels were lower in colorectal cancer patients than in healthy controls [24]. Moreover, in the study of Oberg et al, the serum level of the MMP-2/TIMP-2 complex was significantly lower in CRC patients as compared to healthy blood donors.…”

Section: Discussionsupporting

confidence: 89%

Matrix metalloproteinase 2 and tissue inhibitor of matrix metalloproteinases 2 in the diagnosis of colorectal adenoma and cancer patients.

Groblewska¹,

Mroczko²,

Gryko³

et al. 2011

Folia Histochem Cytobiol.

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Abstract:The aim of the study was to assess the importance of the measurement of matrix metalloproteinase 2 (MMP-2) and tissue inhibitor of matrix metalloproteinases 2 (TIMP-2) in patients with colorectal cancer (CRC) in relation to clinicopathological features of tumor and patients' survival. Additionally, we determined serum MMP-2 and TIMP-2 in colorectal adenoma (CA) patients and healthy controls and compared them with tumor markers, CEA and CA 19-9. The serum levels of MMP-2 and TIMP-2 in 91 CRC patients, 28 CA subjects and 91 healthy controls were determined by ELISA method, but concentrations of CEA and CA 19-9 using MEIA method. Nonparametric statistical analyses were used. Serum levels of MMP-2 and TIMP-2 were significantly lower in CRC patients than in healthy subjects and decreased with tumor stage. Additionally, MMP-2 concentrations were significantly lower in patients with CRC than in CA group. Diagnostic sensitivity of TIMP-2 (59%) was the highest among biomarkers tested and increased in combined use with CEA (79%). Moreover, the area under ROC curve (AUC) of TIMP-2 was larger than AUC of MMP-2 in differentiation between CRC and healthy subjects, but lower than AUC of matrix metalloproteinase 2 in differentiation between colorectal cancer and adenoma. Our findings suggest clinical usefulness of TIMP-2 as a biomarker in the diagnosis of CRC, especially in combination with CEA. However, further investigation is necessary.

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Section: Discussionsupporting

confidence: 89%

Matrix metalloproteinase 2 and tissue inhibitor of matrix metalloproteinases 2 in the diagnosis of colorectal adenoma and cancer patients.

Groblewska¹,

Mroczko²,

Gryko³

et al. 2011

Folia Histochem Cytobiol.

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“…Given that MMP2 0 s upregulation is often associated with loss of the basement membrane type IV collagen (29), reflecting its role in degrading components of the extracellular matrix to facilitate local invasion and disease progression, and that cleavage of laminin-5 by MMP2 may expose a putative cryptic promigratory site on Ln-5, triggering cell motility (30), it was expected that MMP2 would be progressively overexpressed with advancing disease stage, as shown by Li and colleagues (31). However, in support of our observations, and in keeping with the results of our meta-analysis, Waas and colleagues similarly showed that low stage (I and II) disease showed higher MMP2 expression than more advanced stages (III and IV) (32). Interestingly, mRNA levels of MMP2 0 s inhibitor, TIMP1, have been reported to be significantly upregulated in stage IV compared with stages I and II disease (33).…”

Section: Discussionsupporting

confidence: 87%

Absence of MMP2 Expression Correlates with Poor Clinical Outcomes in Rectal Cancer, and Is Distinct from MMP1-Related Outcomes in Colon Cancer

Wong

Chan

Schaeffer

et al. 2011

Clinical Cancer Research

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Purpose: Treatments for colorectal cancer (CRC) are primarily disease stage based. However, heterogeneity in outcome within even a single stage highlights its limitations in predicting disease behavior. Recently, the role of gene expression as predictive and prognostic markers has been explored. Our objectives were to identify consistently differentially expressed genes through meta-analysis of highthroughput gene-expression studies, and evaluate their predictive and prognostic significance in colon (CC) and rectal (RC) cancers.Experimental Design: Publications applying high-throughput gene-expression technologies to specific CRC stages were identified. A vote counting strategy was used to identify the most significant differentially expressed genes. Their predictive and prognostic values were independently assessed in a tissue microarray of 191 cases of stage II-IV CC/RC from two tertiary care centers. Their biological effects were also examined in vitro.Results: MMP1 and MMP2 were identified as consistently underexpressed in liver metastasis compared with primary CRC. Shorter time to distant metastasis and overall survival occurred in stage III CC lacking MMP1 expression, and in stage III RC lacking MMP2. MMP1 levels in stage II and III CC were associated with increased likelihood of distant metastasis, whereas the risk of local recurrence in stage III RC could be stratified by MMP2. Promotion of cell invasion of CRC cell lines exposed to MMP1/2 inhibitors were confirmed in vitro.Conclusions: MMP1 and MMP2 may be useful biomarkers that can help stratify patients at higher risk of developing recurrence in colorectal cancer, and guide individualized treatment decisions to achieve better outcomes.

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“…Moreover, in the study of Oberg et al, the serum levels of the MMP-2/TIMP-2 complexes were significantly lower in CRC patients as compared to healthy blood donors, however, the serum concentrations of free MMP-2 and total amount of TIMP-2 were significantly higher in comparison with control group [28]. Similarly, Waas et al in their study revealed that CRC patients exhibited significantly lower plasma levels of circulating pro-MMP-2 in comparison with healthy controls, independent on technique of determination (zymography versus ELISA method) [29]. Results obtained by Fujimoto and coworkers in gastric and pancreatic cancer patients are similar -they found free and complexed proMMP-2 serum levels to be lower than in healthy subjects [30].…”

Section: Discussionmentioning

confidence: 99%

Serum matrix metalloproteinase 2 and tissue inhibitor of matrix metalloproteinases 2 in esophageal cancer patients

Groblewska¹,

Mroczko²,

Kozłowski³

et al. 2012

Folia Histochem Cytobiol.

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Abstract:The positive expression of MMP-2 and TIMP-2 were found in esophageal cancer (EC) tissue and correlated with cancer stage and clinico-pathological features of tumor and patients' survival. However, little is known about serum levels of those proteins in EC patients. The aim of the present study was to investigate the diagnostic significance of MMP-2 and TIMP-2 serum levels in EC patients in relation to clinico-pathological features of cancer. The study included 53 EC patients and 92 healthy controls. The serum levels of MMP-2, TIMP-2 and classical tumor markers CEA (carcinoembryonic antigen) and SCC (squamous cell carcinoma antigen) were assayed. The prognostic values and diagnostic criteria for the biomarkers tested were defined. Serum levels of MMP-2, TIMP-2 in EC patients were significantly lower, whereas CEA and SCC significantly higher than in control group. The diagnostic sensitivity of TIMP-2 (57%) was higher than those for other biomarkers tested and increased in combination with SCC (70%). Area under ROC curve for TIMP-2 (0.8698) was larger than for other proteins. In Cox's univariate analysis only SCC serum levels were significant prognostic factors for EC patients' survival. The results suggest the limited value of serum analyses of MMP-2 for tumor staging and prognosis in EC and the better usefulness of TIMP-2 than MMP-2 as a tumor marker in the diagnosis of EC, especially in combined use with SCC.

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Plasma Levels of Matrix Metalloproteinase-2 and Tissue Inhibitor of Metalloproteinase-1 Correlate With Disease Stage and Survival in Colorectal Cancer Patients

Abstract: Low pro-matrix metalloproteinase-2 levels and high tissue inhibitor of metalloproteinase-1 levels correlate with parameters of colorectal cancer disease. These correlations may be used in the search for new markers in colorectal cancer diagnosis and prognosis.

Cited by 68 publications

References 33 publications

Matrix metalloproteinase 2 and tissue inhibitor of matrix metalloproteinases 2 in the diagnosis of colorectal adenoma and cancer patients.

Matrix metalloproteinase 2 and tissue inhibitor of matrix metalloproteinases 2 in the diagnosis of colorectal adenoma and cancer patients.

Absence of MMP2 Expression Correlates with Poor Clinical Outcomes in Rectal Cancer, and Is Distinct from MMP1-Related Outcomes in Colon Cancer

Serum matrix metalloproteinase 2 and tissue inhibitor of matrix metalloproteinases 2 in esophageal cancer patients

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