Department of Medical Laboratory Diagnostics, Division of Clinical Chemistry and Laboratory Haematology, Wroclaw Medical University, Borowska 211A, 50-556 Wroclaw, Poland.
Department and Clinic of Thoracic Surgery, Wroclaw Medical University, Grabiszyńska 105, 53-439 Wroclaw, Poland.
Int J Mol Sci. 2023 Jun 24;24(13):10576. doi: 10.3390/ijms241310576.
Matrix metalloproteinase (MMP)-2 and -9 are gelatinases which are capable of degrading type IV collagen and have been linked to cancer invasion and metastatic development. MMP-2 and MMP-9 gene polymorphisms may affect their biological function, and thus their role in cancer development and progression. We analyzed the association of the polymorphism frequencies of -735C/T and -1562C/T with MMP-2 and MMP-9 serum concentrations, as well as their potential effects in lung cancer patients. We conducted a retrospective, case-control study consisting of 112 lung cancer patients and 100 healthy individuals from a Caucasian population in Poland. Polymerase chain reaction with restriction fragment length polymorphism (PCR/RFLP) and electrophoresis was used to genotype genomic DNA from whole blood samples. MMP-2 and MMP-9 serum concentrations were then determined using ELISA. For statistical analysis, Statistica version 13 from TIBCO Software Inc. was utilized with a significance level <0.05. Logistic regression analysis revealed that -735CC (OR = 5.39; 95% CI = 0.62-47.17; = 0.238504) and -735CT genotype (OR = 7.22; 95% CI = 0.78-67.14; = 0.072836), as well as -1562CC (OR = 1.45; 95% CI = 0.31-6.70; = 0.757914) and -1562CT genotype (OR = 1.60; 95% CI = 0.33-7.83; = 0.548801) were associated with a higher risk of lung cancer. There were statistically significant differences observed in the MMP-2 concentration between individuals with the -735CC genotype and the -735CT genotype (non-smoking control: 204.04 ng/mL vs. 237.00 ng/mL, respectively, = 0.041479; adenocarcinoma patients: 157.69 ng/mL vs. 126.37 ng/mL, respectively, = 0.013222), as well as differences in the MMP-9 concentration between individuals with the -1562CC genotype and the -1562CT genotype (smoking control: 385.67 ng/mL vs. 562.80 ng/mL, respectively, = 0.000936; patients with other lung neoplasms: 821.64 ng/mL vs. 928.88 ng/mL, respectively = 0.023315). The role of -735C/T and -1562C/T polymorphisms in an increased risk of lung cancer cannot be dismissed. Specific genotypes affect MMP-2 and MMP-9 concentrations in both lung cancer patients and healthy controls, which may thereby increase lung cancer risk, disease aggressiveness, and patient survival outcomes.
基质金属蛋白酶（MMP）-2 和 -9 是能够降解 IV 型胶原的明胶酶，与癌症侵袭和转移发展有关。MMP-2 和 MMP-9 基因多态性可能影响其生物学功能，从而影响癌症的发生和发展。我们分析了 -735C/T 和 -1562C/T 多态性频率与 MMP-2 和 MMP-9 血清浓度的关联，以及它们在肺癌患者中的潜在作用。我们进行了一项回顾性病例对照研究，包括来自波兰的 112 名肺癌患者和 100 名健康对照者。使用聚合酶链反应-限制性片段长度多态性（PCR/RFLP）和电泳从全血样本中提取基因组 DNA 进行基因分型。然后使用 ELISA 测定 MMP-2 和 MMP-9 血清浓度。统计分析使用 TIBCO Software Inc. 的 Statistica 版本 13，显著性水平<0.05。逻辑回归分析显示，-735CC（OR=5.39；95%CI=0.62-47.17； = 0.238504）和-735CT 基因型（OR=7.22；95%CI=0.78-67.14； = 0.072836），以及-1562CC（OR=1.45；95%CI=0.31-6.70； = 0.757914）和-1562CT 基因型（OR=1.60；95%CI=0.33-7.83； = 0.548801）与肺癌风险增加相关。-735CC 基因型与 -735CT 基因型个体之间的 MMP-2 浓度存在统计学差异（不吸烟对照：204.04ng/mL 比 237.00ng/mL， = 0.041479；腺癌患者：157.69ng/mL 比 126.37ng/mL， = 0.013222），-1562CC 基因型与 -1562CT 基因型个体之间的 MMP-9 浓度也存在统计学差异（吸烟对照：385.67ng/mL 比 562.80ng/mL， = 0.000936；其他肺部肿瘤患者：821.64ng/mL 比 928.88ng/mL， = 0.023315）。-735C/T 和-1562C/T 多态性在增加肺癌风险中的作用不能被忽视。特定基因型会影响肺癌患者和健康对照者的 MMP-2 和 MMP-9 浓度，从而增加肺癌风险、疾病侵袭性和患者生存结局。
