MT1-MMP is not a good prognosticator of cancer survival: evidence from 11 studies

Li, Qiang; Lin, Fuxiang; Li, Jun; Wu, Lu-min; Li, Wei; Yang, Q.

doi:10.1007/s13277-014-2567-8

Cited by 25 publications

(18 citation statements)

References 37 publications

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“…We found that high expression of MMP-14 may be an independent poor prognostic factor (OS, HR = 1.98, 95% Cl: 1.76-2.22, P < 0.001 and DFS/PFS, HR = 3.61, 95% Cl: 2.39-5.43, P < 0.001), particularly in multivariate analysis group (HR = 2.64, 95% CI: 1.95-3.58, P < 0.001), and patients with gastric cancer (HR = 2.21, 95% CI: 1.76-2.77, P < 0.001) and HCC (HR = 2.14, 95% CI: 1.35-2.19, P < 0.001) and oral cancer(HR = 1.69, 95% CI: 1.30-3.20, P < 0.001). Our findings of gastric cancer were consistent with another similar study [64], nevertheless, no correlation was observed between the MMP-14 expression and the prognosis of colorectal cancer.…”

Section: Discussionsupporting

confidence: 92%

Expression of MMP-14 and prognosis in digestive system carcinoma: a meta-analysis and databases validation

Duan¹,

Peng²,

Yin³

et al. 2020

J. Cancer

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Background:The Matrix metalloproteinase-14 (MMP-14) expression has been shown to be overexpressed in different cancers. However, there is no comprehensive quantitative evaluation of the MMP-14 prognostic value in digestive system carcinoma (DSC). The aim of this study is to explore the correlation between the MMP-14 expression and DSC prognosis. Methods: We conducted a meta-analysis to estimate the association strength between MMP-14 expression and prognosis. GEPIA and Kaplan Meier plotters were used to assess overall survival (OS), disease-free survival (DFS)/progression-free survival (PFS) in DSC patients and the differential expression of MMP-14 in DSC tissues and adjacent tissues. Results: A total of 20 studies including 2,519 patients with OS and 438 patients with DFS/PFS data were analyzed in evidence synthesis. Overall, the combined hazard ratio (HR) with 95% confidence interval (95% CI) was 1.98 (95%Cl: 1.77-2.22, P<0.001) for OS and 3.61 (95%Cl: 2.39-5.43, P<0.001) for DFS/PFS. For subgroup analyses, significant correlations were revealed between increased MMP-14 expression and poor OS in patients with gastric cancer (HR=2.21, 95%CI: 1.76-2.77, P<0.001), esophageal carcinoma (HR=2.01, 95%CI: 1.58-2.57, P<0.001), oral cancer (HR = 1.69, 95% CI: 1.30-2.20, P < 0.001) (HR=2.14, 95%CI 1.35-2.19, P<0.001) and hepatocarcinoma. In database verification analyses, the MMP-14 expression levels in normal tissues were significantly higher than that in DSC tissues, and significant associations were observed between high MMP-14 expression levels and poor prognosis. Conclusions:The high expression levels of MMP-14 might predict poor prognosis in DSC. Larger prospective clinical cohort studies are required to validate the prognostic role.

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Section: Discussionsupporting

confidence: 92%

Expression of MMP-14 and prognosis in digestive system carcinoma: a meta-analysis and databases validation

Duan¹,

Peng²,

Yin³

et al. 2020

J. Cancer

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“…MMPs have been identified as up-regulated in GC, either tissues or cell lines, and have also been associated with clinicopathologic features and/or survival including MMP 3 [ 168 ], 7 [ 168 – 170 ], 11 [ 162 , 168 ], 9 [ 168 , 171 , 172 ], 12 [ 168 ], 21 [ 168 , 173 ], MT1 [ 174 – 176 ], 14 [ 177 ], 1 [ 162 ], 2 [ 162 ], and 28 [ 162 ].…”

Section: Emerging Markersmentioning

confidence: 99%

Gastric biomarkers: a global review

et al. 2016

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BackgroundGastric cancer is an aggressive disease with a poor 5-year survival and large global burden of disease. The disease is biologically and genetically heterogeneous with a poorly understood carcinogenesis at the molecular level. Despite the many prognostic, predictive, and therapeutic biomarkers investigated to date, gastric cancer continues to be detected at an advanced stage with resultant poor clinical outcomes.Main bodyThis is a global review of gastric biomarkers with an emphasis on HER2, E-cadherin, fibroblast growth factor receptor, mammalian target of rapamycin, and hepatocyte growth factor receptor as well as sections on microRNAs, long noncoding RNAs, matrix metalloproteinases, PD-L1, TP53, and microsatellite instability.ConclusionA deeper understanding of the pathogenesis and biological features of gastric cancer, including the identification and characterization of diagnostic, prognostic, predictive, and therapeutic biomarkers, hopefully will provide improved clinical outcomes.

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“…Membrane type 1-Matrix Metalloproteinase (MT1-MMP, also known as MMP14) has emerged as an attractive biomarker for tumor-targeted antibody development since this protein is crucial for the progression, invasion, migration and angiogenesis of tumors[ 12 , 13 ]; and specifically, its expression correlates with tumor grade and it is associated with reduced survival in gliomas[ 14 , 15 ] and other cancers[ 16 ]. In addition, a growing body of evidence reveals that overexpression of MT1-MMP plays also a significant role in promoting gliomagenesis[ 17 ].…”

Section: Introductionmentioning

confidence: 99%

Targeting MT1-MMP as an ImmunoPET-Based Strategy for Imaging Gliomas

et al. 2016

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BackgroundA critical challenge in the management of Glioblastoma Multiforme (GBM) tumors is the accurate diagnosis and assessment of tumor progression in a noninvasive manner. We have identified Membrane-type 1 matrix metalloproteinase (MT1-MMP) as an attractive biomarker for GBM imaging since this protein is actively involved in tumor growth and progression, correlates with tumor grade and is closely associated with poor prognosis in GBM patients. Here, we report the development of an immunoPET tracer for effective detection of MT1-MMP in GBM models.MethodsAn anti-human MT1-MMP monoclonal antibody (mAb), LEM2/15, was conjugated to p-isothiocyanatobenzyl-desferrioxamine (DFO-NCS) for 89Zr labeling. Biodistribution and PET imaging studies were performed in xenograft mice bearing human GBM cells (U251) expressing MT1-MMP and non-expressing breast carcinoma cells (MCF-7) as negative control. Two orthotopic brain GBM models, patient-derived neurospheres (TS543) and U251 cells, with different degrees of blood-brain barrier (BBB) disruption were also used for PET imaging experiments.Results89Zr labeling of DFO-LEM2/15 was achieved with high yield (>90%) and specific activity (78.5 MBq/mg). Biodistribution experiments indicated that 89Zr-DFO-LEM2/15 showed excellent potential as a radiotracer for detection of MT1-MMP positive GBM tumors. PET imaging also indicated a specific and prominent 89Zr-DFO-LEM2/15 uptake in MT1-MMP+ U251 GBM tumors compared to MT1-MMP- MCF-7 breast tumors. Results obtained in orthotopic brain GBM models revealed a high dependence of a disrupted BBB for tracer penetrance into tumors. 89Zr-DFO-LEM2/15 showed much higher accumulation in TS543 tumors with a highly disrupted BBB than in U251 orthotopic model in which the BBB permeability was only partially increased. Histological analysis confirmed the specificity of the immunoconjugate in all GBM models.ConclusionA new anti MT1-MMP-mAb tracer, 89Zr-DFO-LEM2/15, was synthesized efficiently. In vivo validation showed high-specific-contrast imaging of MT1-MMP positive GBM tumors and provided strong evidence for utility of MT1-MMP-targeted immunoPET as an alternate to nonspecific imaging of GBM.

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MT1-MMP is not a good prognosticator of cancer survival: evidence from 11 studies

Cited by 25 publications

References 37 publications

Expression of MMP-14 and prognosis in digestive system carcinoma: a meta-analysis and databases validation

Expression of MMP-14 and prognosis in digestive system carcinoma: a meta-analysis and databases validation

Gastric biomarkers: a global review

Targeting MT1-MMP as an ImmunoPET-Based Strategy for Imaging Gliomas

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