Matrix Metalloproteinases as Biomarkers and Treatment Targets in Mesothelioma: A Systematic Review

Our plain-English summary of Matrix Metalloproteinases as Biomarkers and Treatment Targets in Mesothelioma: A Systematic Review, by D. Štrbac, V. Dolžan (Biomolecules, 2021).

The study

• Authors: D. Štrbac, V. Dolžan
• Journal: Biomolecules
• Published: 2021;11(9)
• Type of article: Systematic review
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Metalloproteinases (MMPs) have an important role in tissue remodeling and have been shown to have an effect on tumor progression, invasion, metastasis formation, and apoptosis in several tumors, including mesothelioma. Mesothelioma is a rare tumor arising from pleura and peritoneum and is frequently associated with asbestos exposure. We have performed a systematic search of PubMed.gov and ClinicalTrials.gov databases to retrieve and review three groups of studies: studies of MMPs expression in tumor tissue or body fluids in patients with mesothelioma, studies of MMPs genetic variability, and studies of MMPs as potential novel drug targets in mesothelioma. Several studies of MMPs in mesothelioma tissues reported a link between higher expression levels of commonly studied MMPs and clinical parameters, such as overall survival. Fewer studies have investigated genetic variability of MMP genes. Nevertheless, these studies suggested that certain genetic variants in MMP genes can have either protective or tumor-promoting effects on mesothelioma patients. MMPs have been also reported as novel drug targets, but so far no clinical trials of MMP inhibitors are registered in mesothelioma. In conclusion, MMPs play an important role in mesothelioma, but further studies are needed to elucidate the potentials of MMPs as biomarkers and drug targets in mesothelioma.

In plain English

This article was a systematic review, not a new study of patients. The authors searched PubMed.gov for articles published from 2000 to 2021, and also searched ClinicalTrials.gov. They retrieved 48 papers on matrix metalloproteinases (MMPs), tissue-remodeling enzymes, in mesothelioma. They grouped the papers into three kinds: MMP levels in tumor tissue or body fluids, genetic variants in MMP genes, and MMPs as drug targets. In one reviewed study, blood MMP2 and MMP9 levels did not differ significantly between mesothelioma patients, high-risk asbestos-exposed subjects and healthy subjects. Other reviewed studies reported that higher MMP2 activity, combined with weight loss, was an independent poor prognostic factor, and that MMP14 expression was associated with overall survival. In a genetic study of 236 mesothelioma patients and 161 healthy blood donors, carriers of the MMP2 rs243865 variant had a significantly lower risk of mesothelioma. The authors found no clinical trials of MMP inhibitors in mesothelioma. Inhibitor studies used only cell lines or mouse models. The authors concluded that MMPs may have a role as prognostic biomarkers and potential treatment targets.

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: systematic review of literature in PubMed.gov (limited to 2000 to 2021) and ClinicalTrials.gov
• Who was studied: 48 published papers on MMPs in mesothelioma (human samples or cell lines for biomarker studies; animal models also included for inhibitor studies)
• Exposure: Matrix metalloproteinases (mainly MMP2, MMP9 and MMP14): their expression levels, gene variants, and inhibitors. Asbestos exposure was not itself studied; no fiber types are named.
• Main results:
  • In a reviewed study (Amati et al.) of 22 mesothelioma patients, 94 high-risk asbestos-exposed subjects and 54 healthy subjects, MMP2 and MMP9 levels did not differ significantly between the groups.
  • In a reviewed tissue study (Edwards et al.), higher total and pro-MMP2 activity, in combination with weight loss, reached significance as independent poor prognostic factors.
  • In a reviewed study (Crispi et al.) of 70 mesothelioma patients, MMP14 expression was the only parameter associated with overall survival.
  • In a reviewed genetic study (Strbac et al.) of 236 mesothelioma patients and 161 healthy blood donors, carriers of at least one MMP2 rs243865 variant allele had significantly lower risk for mesothelioma.
  • In a reviewed study of 199 mesothelioma patients, MMP9 rs2250889 was associated with shorter time to progression and overall survival, and MMP9 rs205449 with longer time to progression.
  • The authors found no completed or ongoing clinical trials related to MMPs in mesothelioma.
• The authors' conclusion: The authors concluded that MMP expression and genetic variation may have an important role in mesothelioma as prognostic biomarkers and as potential treatment targets.
• Limitations the authors state:
  • All reviewed studies of MMP inhibitors were done on mesothelioma cell lines or mouse models.
  • The biological role of the MMP9 variants linked to prognosis is unclear, since they were not associated with serum MMP9 levels in a later study.
  • One reviewed tissue study (Edwards et al.) had a low number of samples.

Topics

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

Medical terms in this study, explained in our Lexicon: Biomarker, Mesothelioma, Systematic Review, Metastasis, Apoptosis, Pleura, Peritoneum, Asbestos Exposure.

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