Matrix metalloproteinases polymorphisms as baseline risk predictors in malignant pleural mesothelioma

Štrbac, Danijela; Goričar, Katja; Dolžan, Vita; Kovač, Viljem

doi:10.2478/raon-2018-0005

Cited by 13 publications

(11 citation statements)

References 17 publications

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“…Serum samples were prepared immediately after blood sampling, aliquoted, and stored at −20°C until MMP9 levels were measured. The remaining blood peripheral lymphocytes were used for DNA isolation, and all the patients have been genotyped for common MMP2 , MMP9 , and MMP14 polymorphisms [17].…”

Section: Methodsmentioning

confidence: 99%

“…However, MMP9 and MMP2 as potential biomarkers in MM did not reach diagnostic value as potential standalone biomarkers and more studies are needed to evaluate the role of soluble MMP9 in MM. We have shown that MMP9 rs2250889 CG genotype carriers had significantly shorter overall survival (OS) and time to progression (TTP), while MMP9 rs20544 CT allele carriers had longer OS [17, 18].…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of Matrix Metalloproteinase 9 Serum Concentration as a Biomarker in Malignant Mesothelioma

et al. 2019

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Background. Malignant mesothelioma (MM) is a rare, but fatal disease with few treatment options. The diagnosis and treatment response are challenging in MM. Therefore, the search for novel diagnostic and prognostic biomarkers is ongoing. The aim of our study was to investigate matrix metalloproteinase 9 (MMP9) as a potential serum biomarker of treatment response and survival in MM. We also investigated the influence of genetic polymorphisms on MMP9 serum levels. Methods. We included 110 patients with MM that have been previously genotyped for common MMP9 polymorphisms. Serum samples were collected before treatment, at the end of chemotherapy, and at the time of progression. MMP9 serum levels were measured using enzyme-linked immunosorbent assay kits. The role of serum MMP9 and MMP9 polymorphisms in treatment response was determined using the nonparametric tests and logistic or Cox regression. Results. Median serum MMP9 was 706.7 (499.6-1224.9) ng/ml before treatment, 440.5 (255.9-685.2) ng/ml after chemotherapy, and 502.8 (307.2-851.4) ng/ml at disease progression. After chemotherapy, 87 (79.8%) patients had lower serum MMP9, with the median change of -286.3 (-607.3 to -70.2) ng/ml (P<0.001). At disease progression, 47 (65.3%) patients had lower serum MMP9 compared to pretreatment values, with the median change of -163.7 (-466.6 to 108.6) ng/ml (P=0.001). Patients with higher performance status had higher serum MMP9 before treatment (P=0.010). Among investigated polymorphisms, only rs17576 was associated with serum MMP9 levels before treatment (P=0.041). Conclusion. Median serum MMP9 levels differed significantly before and after treatment of MM, but failed to reach significance as a standalone biomarker. The contribution of MMP9 serum levels and MMP9 polymorphisms to a composite diagnostic and prognostic biomarker should be further tested.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Evaluation of Matrix Metalloproteinase 9 Serum Concentration as a Biomarker in Malignant Mesothelioma

et al. 2019

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“…Three SNPs in MMP2 (rs1053605, rs243849, and rs14070) were selected to identify MMP2 candidate SNP variants based on NCBI database ( https://www.ncbi.nlm.nih.gov/snp ), minor allele frequency (MAF) >5%, and SNP was better assessed in previous studies ( 9 , 18 – 20 ). After the extraction and purification of the above-mentioned sample DNA, primers for candidate SNPs (rs1053605, rs243849 and rs14070) were designed based on the gene sequence of MMP2 using Primer5.0 primer design software ( Supplementary Table 1 ).…”

Section: Methodsmentioning

confidence: 99%

Impact of MMP2 rs243849 and rs14070 genetic polymorphisms on the ischemic stroke susceptibility in Chinese Shaanxi population

Yang

Zhang

et al. 2022

Front. Neurol.

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BackgroundIschemic stroke (IS) is a complex neurological disease affected by genetics and environment. Matrix metalloproteinase-2 (MMP2) is involved in extracellular matrix (ECM) degradation, inflammation and angiogenesis to regulate the development and recovery of IS.PurposesThe aim of this study was to explore the association of rs1053605, rs243849 and rs14070 in MMP2 with the risk of IS in Chinese Shaanxi population.MethodsIn this study, 677 IS patients and 681 normal controls were recruited. Rs1053605, rs243849 and rs14070 in MMP2 were genotyped. Logistic regression analysis was applied to evaluate the association of rs1053605, rs243849 and rs14070 in MMP2 with IS susceptibility and the association of environmental factors with MMP2 genetic susceptibility to IS.ResultsThe results of the overall analysis demonstrated that rs14070 in MMP2 significantly reduced the risk of IS in Chinese Shaanxi population (OR = 0.767, 95% CI = 0.619–0.952, P = 0.016). Subgroup analysis illustrated that rs243849 in MMP2 evidently increased the risk of IS among drinkers, while rs14070 in MMP2 apparently reduced IS susceptibility among females, participants with aged >55, smokers and drinkers.ConclusionsCollectively, rs243849 and rs14070 in MMP2 were significantly associated with the risk of IS in Chinese Shaanxi population, and the effect of MMP2 to IS may be associated with its genetic susceptibility.

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“…In a study that included 236 mesothelioma patients and 161 healthy blood donors, carriers of at least one polymorphic MMP2 rs243865 allele had significantly lower risk for mesothelioma. This association was even more pronounced in patients exposed to asbestos, indicating that this SNP could be used as a potential baseline risk predictor in mesothelioma [ 25 ].…”

Section: Mmps Genetic Variability In Mesotheliomamentioning

confidence: 99%

Matrix Metalloproteinases as Biomarkers and Treatment Targets in Mesothelioma: A Systematic Review

Štrbac

Dolžan

2021

Biomolecules

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Metalloproteinases (MMPs) have an important role in tissue remodeling and have been shown to have an effect on tumor progression, invasion, metastasis formation, and apoptosis in several tumors, including mesothelioma. Mesothelioma is a rare tumor arising from pleura and peritoneum and is frequently associated with asbestos exposure. We have performed a systematic search of PubMed.gov and ClinicalTrials.gov databases to retrieve and review three groups of studies: studies of MMPs expression in tumor tissue or body fluids in patients with mesothelioma, studies of MMPs genetic variability, and studies of MMPs as potential novel drug targets in mesothelioma. Several studies of MMPs in mesothelioma tissues reported a link between higher expression levels of commonly studied MMPs and clinical parameters, such as overall survival. Fewer studies have investigated genetic variability of MMP genes. Nevertheless, these studies suggested that certain genetic variants in MMP genes can have either protective or tumor-promoting effects on mesothelioma patients. MMPs have been also reported as novel drug targets, but so far no clinical trials of MMP inhibitors are registered in mesothelioma. In conclusion, MMPs play an important role in mesothelioma, but further studies are needed to elucidate the potentials of MMPs as biomarkers and drug targets in mesothelioma.

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Matrix metalloproteinases polymorphisms as baseline risk predictors in malignant pleural mesothelioma

Cited by 13 publications

References 17 publications

Evaluation of Matrix Metalloproteinase 9 Serum Concentration as a Biomarker in Malignant Mesothelioma

Evaluation of Matrix Metalloproteinase 9 Serum Concentration as a Biomarker in Malignant Mesothelioma

Impact of MMP2 rs243849 and rs14070 genetic polymorphisms on the ischemic stroke susceptibility in Chinese Shaanxi population

Matrix Metalloproteinases as Biomarkers and Treatment Targets in Mesothelioma: A Systematic Review

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