Analysis of MMP-2-735C/T (rs2285053) and MMP-9-1562C/T (rs3918242) Polymorphisms in the Risk Assessment of Developing Lung Cancer

Abstract

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 MMP-2-735C/T and MMP-9-1562C/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 MMP-2-735CC (OR = 5.39; 95% CI = 0.62–47.17; p = 0.238504) and -735CT genotype (OR = 7.22; 95% CI = 0.78–67.14; p = 0.072836), as well as MMP-9-1562CC (OR = 1.45; 95% CI = 0.31–6.70; p = 0.757914) and -1562CT genotype (OR = 1.60; 95% CI = 0.33–7.83; p = 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, p = 0.041479; adenocarcinoma patients: 157.69 ng/mL vs. 126.37 ng/mL, respectively, p = 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, p = 0.000936; patients with other lung neoplasms: 821.64 ng/mL vs. 928.88 ng/mL, respectively p = 0.023315). The role of MMP-2-735C/T and MMP-9 -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.

Enhancing the revelation of key genes and interaction networks in non‐small cell lung cancer with major depressive disorder: A bioinformatics analysis

“…Despite limited research on hub gene‐related pathways such as regulation of coagulation and the relaxin signaling pathway in NSCLC and MDD, there is a wealth of studies on interacting TFs. MMP9 serves as the site of action for multiple TFs in our study, plays a pivotal role in collagen degradation, 76 basement membrane degradation, inflammation regulation. The MMP9 has been extensively studied and its close association with proliferation, migration, and invasion has been well‐documented, primarily implicated in the metastasis of NSCLC.…”