Clinical significance of serum levels of matrix metalloproteinase 2 (MMP-2) and its tissue inhibitor (TIMP-2) in gastric cancer

Mroczko, Barbara; Łukaszewicz-Zając, Marta; Gryko, Mariusz; Kędra, Bogusław; Szmitkowski, Maciej

doi:10.5603/fhc.2011.0018

Cited by 24 publications

(14 citation statements)

References 27 publications

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“…Serum concentrations of MMP-2 and TIMP-2 in cancer group were significantly lower than in healthy controls. The obtained results are in accordance with our previous studies on colorectal [25] and gastric cancer [26] and with results of other authors who examined serum or plasma levels of those proteins in malignancies of alimentary tract, e.g. colorectal cancer [27].…”

Section: Discussionsupporting

confidence: 82%

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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Section: Discussionsupporting

confidence: 82%

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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“…31 In general, MMP2 may promote the cleavage of extracellular matrix proteins, leading to the destruction of the basal membrane as well as tumor cell invasion into the connective tissue matrix, thereby resulting in tumor metastasis in GC. 13 In short, the current meta-analysis indicated that MMP2 protein expression may play an important role in the development of GC, suggesting that detection of MMP2 expression may be utilized as an independent prognostic marker for GC.…”

Section: Discussionmentioning

confidence: 94%

“…14 In addition, there is evidence that suggests that an elevated MMP2 level is significantly related to increased tumor metastasis and advanced stomach cancer. 13,15 More importantly, high levels of MMP2 expression in tissue and plasma are strongly correlated with the depth of tumor infiltration, and the severity of lymph node metastasis, distant metastasis, Union International Contre le Cancer (UICC) stage, and poor overall survival (OS). This could be an indication that MMP2 expression could be of value as a prognostic marker for GC patients.…”

Section: Introductionmentioning

confidence: 99%

“…10,11 Due to its ability to degrade the basal membrane, MMP2 has been intensively hypothesized to be a potential marker in tumor progression and prognosis in several different kinds of malignancies, such as ovarian cancer, lung carcinoma, as well as GC. 12,13 It has been widely reported that MMP2 is expressed in a large number of cell types, and overexpressed in a wide variety of human cancers, including GC. 14 In addition, there is evidence that suggests that an elevated MMP2 level is significantly related to increased tumor metastasis and advanced stomach cancer.…”

Section: Introductionmentioning

confidence: 99%

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Relationships Between Abnormal MMP2 Expression and Prognosis in Gastric Cancer: A Meta-Analysis of Cohort Studies

Wang

Zhou

Liu

2014

Cancer Biotherapy and Radiopharmaceuticals

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We carried out this current meta-analysis of relevant cohort studies in an attempt to investigate the relationships between abnormal matrix metalloproteinases-2 (MMP2) expression and gastric cancer (GC) prognosis. A range of electronic databases were searched for relevant articles without any language restrictions: Web of Science (1945-2013), the Cochrane Library Database (Issue 12, 2013), PubMed (1966-2013), EMBASE (1980-2013), CINAHL (1982-2013), and the Chinese Biomedical Database (CBM) (1982-2013). Meta-analysis was conducted using the STATA 12.0 software. Crude hazard ratios (HRs), with 95% confidence intervals (95% CIs), were calculated. Ten clinical cohort studies with a total of 1669 GC patients were included in this meta-analysis. The results of our meta-analysis suggested that MMP2-positive patients display a shorter overall survival (OS) than MMP2-negative patients (HR=1.31, 95% CI=0.98-1.63, p<0.001). Subgroup analysis based on ethnicity revealed that abnormal MMP2 expression was associated with significantly worse OS in patients with GC among both Caucasian and Asian populations (all p<0.05). Our meta-analysis indicated that abnormal MMP2 expression may be strongly correlated with poor prognosis in patients with GC. Thus, MMP2 expression may serve as an independent prognostic factor for GC.

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“…Likewise, elevated levels of MMP-2 and TIMP-2 have been correlated to distant metastasis in serum samples. [105] The incidence of high levels of MMP14 in bone marrow and peripheral blood detected by qPCR has been correlated with peritoneal dissemination. [101] The expression of MMP7 (mRNA/protein) in tumor specimens detected by RT-PCR and immunohistochemistry has also been associated with this parameter.…”

Section: Matrix Metalloproteinases and Their Tissue Inhibitors In Gasmentioning

confidence: 99%

Matrix metalloproteinases and their tissue inhibitors in gastric cancer as molecular markers

Sampieri¹,

León-Córdoba²,

Troche³

2013

J Can Res Ther

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Gastric cancer is a complex disease that involves a range of biological individuals and tumors with histopathological features. The pathogenesis of this disease is multi-factorial and includes the interaction of genetic predisposition with environmental factors. Gastric cancer is normally diagnosed in advanced stages where there are few alternatives to offer and the prognosis is difficult to establish. Metastasis is the leading cause of cancer deaths. Identification of key genes and signaling pathways involved in metastasis and recurrence could predict these events and thereby identify therapeutic targets. In this context, the extracellular matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) represent a potential prognostic tool, because both genetic families regulate growth, angiogenesis, invasion, immune response, epithelial mesenchymal transition and cellular survival. Proteolytic parameters based on MMP/TIMP expression could be useful in the identification of patients with a high probability of developing distant metastases or peritoneal dissemination for each degree of histological malignancy. It is also probable that these parameters can allow improvement in the extent of surgery and dictate the most suitable therapy. We reviewed papers focused on human gastric epithelial cancer as a model and focus on the potential use of MMPs and TIMPs as molecular markers; also we include literature regarding gastric cancer risk factors, classification systems and MMP/TIMP regulation.

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Clinical significance of serum levels of matrix metalloproteinase 2 (MMP-2) and its tissue inhibitor (TIMP-2) in gastric cancer

Cited by 24 publications

References 27 publications

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

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

Relationships Between Abnormal MMP2 Expression and Prognosis in Gastric Cancer: A Meta-Analysis of Cohort Studies

Matrix metalloproteinases and their tissue inhibitors in gastric cancer as molecular markers

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