Matrix Metalloproteinases Polymorphisms as Prognostic Biomarkers in Malignant Pleural Mesothelioma.

Danijela Štrbac,Katja Goričar,Vita Dolžan,Viljem Kovač

doi:10.1155/2017/8069529

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.

Highlights

Malignant pleural mesothelioma (MPM) is a rare disease, linked to asbestos exposure in more than 80% of the cases
The Slovenian national registry follows the data on mesothelioma since 1961, and the current incidence is about 43 new cases per year in a population of roughly 2 million [2]
The distributions of all the investigated single nucleotide polymorphisms (SNPs) were in agreement with the HW equilibrium

Summary

Introduction

Malignant pleural mesothelioma (MPM) is a rare disease, linked to asbestos exposure in more than 80% of the cases. The standard treatment of mesothelioma has not changed It relies on surgery, chemotherapy, and radiation-based approaches [3]. In Slovenia, chemotherapy with cisplatin doublets became a standard part of multimodal treatment in 2003 This led to improved median survival of 13.6 months, as reported in a population-based survey of 444 Slovenian MPM patients [4]. 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).

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