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Association of MMP9-1562C/T and MMP13-77A/G Polymorphisms with Non-Small Cell Lung Cancer in Southern Chinese Population

Background: Matrix metalloproteinases (MMPs) are capable of degrading and modifying most components of the extracellular matrix (ECM) and the basal membrane (BM), and play crucial roles in cancer invasion and metastasis. MMP gene expressions were regulated primarily at the transcriptional level, whi...

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Autores principales: Li, Wen, Jia, Ming Xi, Wang, Jian Hui, Lu, Jie Li, Deng, Jing, Tang, Jian Xin, Liu, Cun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6468416/
https://www.ncbi.nlm.nih.gov/pubmed/30889876
http://dx.doi.org/10.3390/biom9030107
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author Li, Wen
Jia, Ming Xi
Wang, Jian Hui
Lu, Jie Li
Deng, Jing
Tang, Jian Xin
Liu, Cun
author_facet Li, Wen
Jia, Ming Xi
Wang, Jian Hui
Lu, Jie Li
Deng, Jing
Tang, Jian Xin
Liu, Cun
author_sort Li, Wen
collection PubMed
description Background: Matrix metalloproteinases (MMPs) are capable of degrading and modifying most components of the extracellular matrix (ECM) and the basal membrane (BM), and play crucial roles in cancer invasion and metastasis. MMP gene expressions were regulated primarily at the transcriptional level, which was associated with tumor spread and patient prognosis. Polymorphisms in MMPs have been reported to be associated with non-small cell lung cancer (NSCLC). The objective of this study aim to evaluate the serum levels and polymorphisms of MMP-9 and MMP-13 in non-small cell lung cancer patients compared to normal subjects and their correlation to non-small cell lung cancer histopathology findings in Southern Chinese people. Methods: This case–control study included 245 patients with NSCLC and 258 healthy controls. Genomic DNA was extracted by using DNA extraction kit, genotyping was confirmed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct DNA sequencing, and serum levels of MMP-9 and MMP-13 were measured by using a specific ELISA, Human Matrix Metalloproteinase Enzyme Immunoassay Kits. Statistical analysis was carried out using the SPSS 23.0 software package. Results: The subjects carrying the TT genotype had a decreased risk of lung cancer in MMP9-1562C/T comparing with the CC genotype (p = 0.00, OR = 0.45, 95% CI = 0.29–0.68), and the MMP13-77 AA genotype was associated with a decreased risk of NSCLC by comparing with the GG genotype (p = 0.03, OR = 0.56, 95% CI = 0.33–0.94). Moreover, the C allele of MMP9-1562C/T could increase serum level of NSCLC in compared with the A allele (OR = 1.19, 95% CI = 0.75–1.89). Similarly, the AA genotype of MMP13 might be a marker of decreased serum level of lung cancer (OR = 0.76, 95% CI = 0.51–1.14). Conclusions: The results of these analyses underline the support of the notion that the CC genotype of MMP9-1562C/T and GG genotypes of MMP13-77G/A were associated with the increased risk NSCLC, and the serum levels of MMP9 and MMP13 were consistent with the results of the SNP analysis. MMP13 and MMP9 might be function as a key oncogene in NSCLC with a Southern Chinese population. Combined detection of SNP and enzyme activity between MMP9 and MMP13 are expected to be a potential diagnostic method of non-small cell lung cancer.
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spelling pubmed-64684162019-04-24 Association of MMP9-1562C/T and MMP13-77A/G Polymorphisms with Non-Small Cell Lung Cancer in Southern Chinese Population Li, Wen Jia, Ming Xi Wang, Jian Hui Lu, Jie Li Deng, Jing Tang, Jian Xin Liu, Cun Biomolecules Article Background: Matrix metalloproteinases (MMPs) are capable of degrading and modifying most components of the extracellular matrix (ECM) and the basal membrane (BM), and play crucial roles in cancer invasion and metastasis. MMP gene expressions were regulated primarily at the transcriptional level, which was associated with tumor spread and patient prognosis. Polymorphisms in MMPs have been reported to be associated with non-small cell lung cancer (NSCLC). The objective of this study aim to evaluate the serum levels and polymorphisms of MMP-9 and MMP-13 in non-small cell lung cancer patients compared to normal subjects and their correlation to non-small cell lung cancer histopathology findings in Southern Chinese people. Methods: This case–control study included 245 patients with NSCLC and 258 healthy controls. Genomic DNA was extracted by using DNA extraction kit, genotyping was confirmed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct DNA sequencing, and serum levels of MMP-9 and MMP-13 were measured by using a specific ELISA, Human Matrix Metalloproteinase Enzyme Immunoassay Kits. Statistical analysis was carried out using the SPSS 23.0 software package. Results: The subjects carrying the TT genotype had a decreased risk of lung cancer in MMP9-1562C/T comparing with the CC genotype (p = 0.00, OR = 0.45, 95% CI = 0.29–0.68), and the MMP13-77 AA genotype was associated with a decreased risk of NSCLC by comparing with the GG genotype (p = 0.03, OR = 0.56, 95% CI = 0.33–0.94). Moreover, the C allele of MMP9-1562C/T could increase serum level of NSCLC in compared with the A allele (OR = 1.19, 95% CI = 0.75–1.89). Similarly, the AA genotype of MMP13 might be a marker of decreased serum level of lung cancer (OR = 0.76, 95% CI = 0.51–1.14). Conclusions: The results of these analyses underline the support of the notion that the CC genotype of MMP9-1562C/T and GG genotypes of MMP13-77G/A were associated with the increased risk NSCLC, and the serum levels of MMP9 and MMP13 were consistent with the results of the SNP analysis. MMP13 and MMP9 might be function as a key oncogene in NSCLC with a Southern Chinese population. Combined detection of SNP and enzyme activity between MMP9 and MMP13 are expected to be a potential diagnostic method of non-small cell lung cancer. MDPI 2019-03-18 /pmc/articles/PMC6468416/ /pubmed/30889876 http://dx.doi.org/10.3390/biom9030107 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Li, Wen
Jia, Ming Xi
Wang, Jian Hui
Lu, Jie Li
Deng, Jing
Tang, Jian Xin
Liu, Cun
Association of MMP9-1562C/T and MMP13-77A/G Polymorphisms with Non-Small Cell Lung Cancer in Southern Chinese Population
title Association of MMP9-1562C/T and MMP13-77A/G Polymorphisms with Non-Small Cell Lung Cancer in Southern Chinese Population
title_full Association of MMP9-1562C/T and MMP13-77A/G Polymorphisms with Non-Small Cell Lung Cancer in Southern Chinese Population
title_fullStr Association of MMP9-1562C/T and MMP13-77A/G Polymorphisms with Non-Small Cell Lung Cancer in Southern Chinese Population
title_full_unstemmed Association of MMP9-1562C/T and MMP13-77A/G Polymorphisms with Non-Small Cell Lung Cancer in Southern Chinese Population
title_short Association of MMP9-1562C/T and MMP13-77A/G Polymorphisms with Non-Small Cell Lung Cancer in Southern Chinese Population
title_sort association of mmp9-1562c/t and mmp13-77a/g polymorphisms with non-small cell lung cancer in southern chinese population
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6468416/
https://www.ncbi.nlm.nih.gov/pubmed/30889876
http://dx.doi.org/10.3390/biom9030107
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