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

Our plain-English summary of Evaluation of Matrix Metalloproteinase 9 Serum Concentration as a Biomarker in Malignant Mesothelioma, by D. Štrbac, K. Goričar, V. Dolžan, et al (Disease Markers, 2019).

The study

• Authors: D. Štrbac, K. Goričar, V. Dolžan, V. Kovač
• Journal: Disease Markers
• Published: 2019;2019:1242964
• Cited by: 7 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

In plain English

This retrospective study from Slovenia tested whether a blood protein called matrix metalloproteinase 9 (MMP9) could show treatment response and survival in malignant mesothelioma. It included 110 patients with pleural or peritoneal mesothelioma diagnosed and treated between 2007 and 2016, all treated with chemotherapy. Of these, 86 were recorded as asbestos-exposed. MMP9 was measured in blood serum before treatment, at the end of chemotherapy, and at disease progression. Median MMP9 was 706.7 ng/ml before treatment, 440.5 ng/ml after chemotherapy, and 502.8 ng/ml at progression. After chemotherapy, 87 of 109 patients with a sample (79.8%) had lower levels than before treatment. Patients with higher ECOG performance status scores, meaning more limited daily activity, had higher levels before treatment. MMP9 levels were not significantly associated with treatment response, time to progression or overall survival. Among the MMP9 gene variants tested, only rs17576 was associated with levels before treatment. The authors concluded that MMP9 might work better combined with other markers than on its own. They noted a relatively small sample and a lack of tumor tissue data.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective study of serum MMP9 levels measured over time, together with MMP9 gene variants (polymorphisms), in mesothelioma patients
• Who was studied: 110 patients with histologically proven pleural or peritoneal malignant mesothelioma diagnosed and treated between 2007 and 2016 in Slovenia (University Clinic Golnik, University Clinic Ljubljana, Institute of Oncology Ljubljana). All received chemotherapy.
• Exposure: The study's main measures were serum MMP9 levels and MMP9 gene variants, not asbestos. Asbestos exposure was recorded only as a patient characteristic: 86 (78.2%) exposed and 24 (21.8%) not exposed. Pretreatment MMP9 did not differ significantly between the two groups (P = 0.625). No fiber types, jobs or doses were given.
• Main results:
  • Serum samples after chemotherapy were available for 109 of the 110 patients. Samples at disease progression were available for 72 of the 95 patients whose disease progressed.
  • Median serum MMP9 across all patients 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%) of the 109 patients with a post-chemotherapy sample had lower MMP9 than before treatment, with a median change of -286.3 (-607.3 to -70.2) ng/ml (P less than 0.001).
  • At disease progression, 47 (65.3%) of the 72 patients with a progression sample had lower MMP9 than before treatment, with a median change of -163.7 (-466.6 to 108.6) ng/ml.
  • MMP9 levels were significantly higher at disease progression than after chemotherapy (P = 0.006).
  • Patients with higher ECOG performance status scores had higher pretreatment MMP9 (P = 0.010). Median levels were 466.7 ng/ml for ECOG 0 and 1026.5 ng/ml for ECOG 2.
  • Higher MMP9 levels were not associated with better treatment response (OR = 1.34, 95% CI = 0.50-3.58, P = 0.559).
  • For the gene variant rs17576, the 8 patients carrying two G alleles had significantly higher pretreatment MMP9 than the 45 patients carrying two A alleles (P = 0.013). No other variant tested was associated with MMP9 levels.
  • MMP9 levels before treatment, after treatment and at disease progression showed no statistically significant association with time to progression or overall survival, even after adjustment for clinical factors.
• The authors' conclusion: The authors concluded that MMP9 levels correlate with ECOG performance status and that the rs17576 variant influences MMP9 levels in mesothelioma patients. They believed MMP9 could be more useful as part of a composite biomarker with other novel markers than on its own.
• Limitations the authors state:
  • Relatively small sample size, due to the rarity of mesothelioma
  • No comparative data on MMP9 levels in tumor tissue

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma, Peritoneal mesothelioma.

Medical terms in this study, explained in our Lexicon: Biomarker, Mesothelioma, Chemotherapy, Disease Progression, Performance Status.

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