Matrix Metalloproteinases Polymorphisms as Prognostic Biomarkers in Malignant Pleural Mesothelioma

Our plain-English summary of Matrix Metalloproteinases Polymorphisms as Prognostic Biomarkers in Malignant Pleural Mesothelioma, by D. Štrbac, K. Goričar, V. Dolžan, et al (Disease Markers, 2017).

The study

• Authors: D. Štrbac, K. Goričar, V. Dolžan, V. Kovač
• Journal: Disease Markers
• Published: 2017;2017:8069529
• Cited by: 10 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Malignant pleural mesothelioma (MPM) is a rare disease with a relatively short overall survival (OS). Metalloproteinases (MMPs) have a vast biological effect on tumor progression, invasion, metastasis formation, and apoptosis. MMP expression was previously associated with survival in MPM. Our aim was to evaluate if genetic variability of MMP genes could also serve as a prognostic biomarker in MPM.

Methods: We genotyped 199 MPM patients for ten polymorphisms: rs243865, rs243849 and rs7201, in MMP2; rs17576, rs17577, rs20544, and rs2250889 in MMP9; and rs1042703, rs1042704, and rs743257 in MMP14. We determined the influence on survival using Cox regression.

Results: Carriers of polymorphic MMP9 rs2250889 allele had shorter time to progression (TTP) (6.07 versus 10.03 months, HR = 2.45, 95% CI = 1.45-4.14, p = 0.001) and OS (9.23 versus 19.2 months, HR = 2.39, 95% CI = 1.37-4.18, p = 0.002). In contrast, carriers of at least one polymorphic MMP9 rs20544 allele had longer TTP (10.93 versus 9.40 months, HR = 0.57, 95% CI = 0.38-0.86 p = 0.007) and OS (20.67 versus 13.50 months, HR = 0.56, 95% CI = 0.37-0.85, p = 0.007). MMP14 rs1042703 was associated with nominally shorter TTP (8.7 versus 9.27 months, HR = 2.09, 95% CI = 1.06-4.12, p = 0.032).

Conclusions: Selected MMP SNPs were associated with survival and could be used as potential genetic biomarkers in MPM.

In plain English

This retrospective study from Slovenia tested whether common inherited variants in three genes for enzymes called matrix metalloproteinases (MMP2, MMP9 and MMP14) were linked to survival in mesothelioma. The authors analyzed blood DNA from 199 patients diagnosed and treated between 2007 and 2015. Most had pleural mesothelioma, but 18 had peritoneal mesothelioma. Ten variants were tested. The authors called p values up to 0.01 significant and those between 0.01 and 0.05 nominally significant. The 18 carriers of one MMP9 variant (rs2250889) had median overall survival of 9.23 months, against 19.10 months for non-carriers (hazard ratio 2.39, 95% CI 1.37 to 4.18). Carriers of another MMP9 variant (rs20544) lived longer, 19.3 versus 13.5 months (hazard ratio 0.61, 95% CI 0.41 to 0.90), which was nominally significant. Patients with two copies of an MMP14 variant (rs1042703) had shorter survival, also nominally significant. MMP2 variants showed no statistically significant association. The authors concluded that selected variants could be valuable prognostic biomarkers. They noted the small sample and the lack of a replication study.

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 inherited gene variants (genotyping) and survival in mesothelioma patients
• Who was studied: 199 consecutive mesothelioma patients treated mostly at the Institute of Oncology, Ljubljana, Slovenia, diagnosed 2007 to 2015. There were 151 men and 48 women, median age 66. 18 had peritoneal mesothelioma. 150 were recorded as asbestos-exposed and 43 as not exposed (6 missing).
• Exposure: Ten inherited gene variants (single nucleotide polymorphisms) in the MMP2, MMP9 and MMP14 genes, measured from blood DNA. Asbestos exposure was recorded but was not the factor analyzed.
• Main results:
  • Time to progression, MMP9 rs2250889: carriers had a median of 6.07 months versus 10.03 months for non-carriers (HR 2.45, 95% CI 1.45 to 4.14, p 0.001). After adjustment for histological type, weight loss and performance status: HR 2.32, 95% CI 1.34 to 4.03, p 0.003.
  • Overall survival, MMP9 rs2250889: carriers had a median of 9.23 months versus 19.10 months for non-carriers (HR 2.39, 95% CI 1.37 to 4.18, p 0.002). After adjustment: HR 2.52, 95% CI 1.42 to 4.46, p 0.002. Only 18 patients (9.0%) carried this variant.
  • Time to progression, MMP9 rs20544: carriers of at least one variant allele had a median of 10.13 months versus 7.53 months for non-carriers (HR 0.63, 95% CI 0.43 to 0.91, p 0.015). After adjustment: HR 0.62, 95% CI 0.43 to 0.92, p 0.016, which is nominally significant.
  • Overall survival, MMP9 rs20544: carriers had a median of 19.3 months versus 13.5 months for non-carriers (HR 0.61, 95% CI 0.41 to 0.90, p 0.014). After adjustment: HR 0.63, 95% CI 0.42 to 0.95, p 0.025, which is nominally significant.
  • Overall survival, MMP14 rs1042703: patients with two variant alleles had a median of 12.7 months versus 17.5 months for those with the wild-type alleles (HR 1.92, 95% CI 1.02 to 3.06, p 0.043). After adjustment: HR 2.14, 95% CI 1.12 to 4.0, p 0.020, which is nominally significant. For time to progression, carriers showed a nominally significant shorter time only after adjustment (HR 1.44, 95% CI 1.01 to 2.03).
  • The MMP2 variants showed no statistically significant association with time to progression or overall survival.
  • Two rare MMP9 haplotypes carrying the rs2250889 variant (AGGC and AGAC) were associated with shorter time to progression and overall survival.
• The authors' conclusion: The authors concluded that selected MMP gene variants could be valuable prognostic biomarkers in malignant pleural mesothelioma, and that further studies are needed.
• Limitations the authors state:
  • The sample was small, and the authors did not perform a genome-wide association study or a replication study.
  • The results need to be validated in an independent population.

Topics

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

Medical terms in this study, explained in our Lexicon: Biomarker, Pleural Mesothelioma, Overall Survival, Metastasis, Apoptosis.

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• Is a single nucleotide polymorphism a risk factor for lung cancer in the matrix metalloproteinase-2 promoter? — B. Ayşegül, G.H. Veysi, et al. (2011)
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• Inhibition of malignant mesothelioma cell matrix metalloproteinase production and invasion by a novel nutrient mixture — M.W. Roomi, V. Ivanov, et al. (2006)
• Genetic polymorphisms in aquaporin 1 as risk factors for malignant mesothelioma and biomarkers of response to cisplatin treatment — B. Senk, K. Goricar, et al. (2019)
• Matrix Metalloproteinases Polymorphisms as Baseline Risk Predictors in Malignant Pleural Mesothelioma — D. Strbac, K. Goricar, et al. (2018)

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