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Implantation and Monitoring by PET/CT of an Orthotopic Model of Human Pleural Mesothelioma in Athymic Mice
Published on: December 21, 2019
Matrix Metalloproteinases Polymorphisms as Prognostic Biomarkers in Malignant Pleural Mesothelioma
Danijela Štrbac1, Katja Goričar2, Vita Dolžan2
1Institute of Oncology Ljubljana, Ljubljana, Slovenia.
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.
Insights
Genetic variations in matrix metalloproteinase (MMP) genes impact survival for malignant pleural mesothelioma (MPM) patients. Specific MMP9 polymorphisms are linked to altered time to progression and overall survival, suggesting their potential as prognostic biomarkers.
Area of Science:
- Oncology
- Genetics
- Biomarkers
Background:
- Malignant pleural mesothelioma (MPM) is a rare cancer with poor prognosis.
- Matrix metalloproteinases (MMPs) play a role in cancer progression and have been linked to survival in MPM.
- The prognostic value of genetic variations in MMP genes in MPM remains to be fully elucidated.
Purpose of the Study:
- To investigate the association between genetic variability in MMP2, MMP9, and MMP14 genes and patient survival in MPM.
- To evaluate the potential of MMP single nucleotide polymorphisms (SNPs) as prognostic biomarkers for MPM.
Main Methods:
- Genotyping of ten polymorphisms in MMP2, MMP9, and MMP14 genes in 199 MPM patients.
- Analysis of the association between identified polymorphisms and survival outcomes (Time to Progression and Overall Survival).
- Statistical analysis using Cox regression to determine the influence of genetic variations on survival.
Main Results:
- The MMP9 rs2250889 polymorphism was associated with significantly shorter Time to Progression (TTP) and Overall Survival (OS).
- Conversely, the MMP9 rs20544 polymorphism was linked to significantly longer TTP and OS.
- The MMP14 rs1042703 polymorphism showed a trend towards shorter TTP.
Conclusions:
- Specific single nucleotide polymorphisms (SNPs) in MMP genes, particularly MMP9, are associated with survival outcomes in MPM.
- These identified MMP SNPs demonstrate potential as predictive genetic biomarkers for MPM prognosis.
- Further research can explore the clinical utility of these genetic markers in MPM patient management.
