基质金属蛋白酶 9-1562C/T 和基质金属蛋白酶 13-77A/G 多态性与华南地区非小细胞肺癌的相关性研究。
Association of MMP9-1562C/T and MMP13-77A/G Polymorphisms with Non-Small Cell Lung Cancer in Southern Chinese Population.
机构信息
Key Laboratory of Biological Nanomaterials and Devices, College of Life Sciences and Chemistry, Hunan University of Technology, Zhuzhou 412007, China.
National Engineering Laboratory for Rice and Byproducts Deep Processing, College of Food Science and Engineering, Central South University of Forestry and Technology, Changsha 410004, China.
出版信息
Biomolecules. 2019 Mar 18;9(3):107. doi: 10.3390/biom9030107.
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 ( = 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 ( = 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.
背景
基质金属蛋白酶（MMPs）能够降解和修饰细胞外基质（ECM）和基底膜（BM）的大多数成分，在癌症侵袭和转移中发挥关键作用。MMP 基因表达主要在转录水平上受到调控，与肿瘤扩散和患者预后相关。已有报道称 MMP 多态性与非小细胞肺癌（NSCLC）有关。本研究旨在评估 MMP-9 和 MMP-13 在非小细胞肺癌患者与正常对照者中的血清水平和多态性，并分析其与中国南方人群非小细胞肺癌组织病理学发现的相关性。
方法
本病例对照研究纳入了 245 例 NSCLC 患者和 258 例健康对照者。采用 DNA 提取试剂盒提取基因组 DNA，聚合酶链反应-限制性片段长度多态性（PCR-RFLP）和直接 DNA 测序法进行基因分型，采用特定的 ELISA、人基质金属蛋白酶酶免疫分析试剂盒测定 MMP-9 和 MMP-13 的血清水平。采用 SPSS 23.0 软件包进行统计学分析。
结果
与 CC 基因型相比，MMP9-1562C/T 中的 TT 基因型受试者患肺癌的风险降低（ = 0.00，OR = 0.45，95%CI = 0.29⁻0.68），MMP13-77AA 基因型与 NSCLC 风险降低相关（ = 0.03，OR = 0.56，95%CI = 0.33⁻0.94）。此外，与 A 等位基因相比，MMP9-1562C/T 的 C 等位基因可增加 NSCLC 的血清水平（OR = 1.19，95%CI = 0.75⁻1.89）。同样，MMP13 的 AA 基因型可能是肺癌血清水平降低的标志物（OR = 0.76，95%CI = 0.51⁻1.14）。
结论
这些分析结果支持以下观点，即 MMP9-1562C/T 的 CC 基因型和 MMP13-77G/A 的 GG 基因型与 NSCLC 风险增加相关，并且 MMP9 和 MMP13 的血清水平与 SNP 分析结果一致。MMP13 和 MMP9 可能作为中国南方人群 NSCLC 的关键癌基因发挥作用。联合检测 MMP9 和 MMP13 的 SNP 和酶活性有望成为非小细胞肺癌的一种潜在诊断方法。
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