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

Abstract

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.

Inhibition of the Histone Methyltransferase EZH2 Enhances Protumor Monocyte Recruitment in Human Mesothelioma Spheroids

“…These results suggest that Mo-TAMs modulate the remodeling of the extracellular matrix, creating a TME that is more permissive for tumor cell invasion. In support of this hypothesis, we observed that Mo-TAMs triggered a strong induction of MMP9 expression by MPM cells and clinical studies have reported that high expression of MMP9 correlates with a more aggressive MPM phenotype and decreased patients' survival [56,57].…”

Association between matrix metalloproteinase-9 gene polymorphism and breast cancer in Brazilian women

“…It is noteworthy that there is evidence indicating that MMP-9 (rs17576) genotypes and haplotypes affect MMP-9 expression in obese children and in patients of African descent, suggesting that they may exert different effects, resulting in different and varied pathologies (7,22). Moreover, Štrbac et al suggest that serum MMP9 levels and polymorphisms should be studied as possible diagnostic and prognostic biomarkers for malignant mesothelioma (23). A significant difference was observed in the incidence of the rs17576 GG genotype between the case and control groups (po0.003).…”

Level of mesothelin expression can indicate the prognosis of malignant pleural mesothelioma

“…In nowadays, several molecules, including estrogen receptors ( 5 ), matrix metalloproteinase 2 and 9 ( 6 , 7 ) have been reported as biomarkers for MPM. However, these factors were not available for early diagnosis due to lack of specificity.…”