Institute of Oncology Ljubljana, Ljubljana, Slovenia.
Pharmacogenetics Laboratory, Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
Dis Markers. 2017;2017:8069529. doi: 10.1155/2017/8069529. Epub 2017 Sep 12.
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 genes could also serve as a prognostic biomarker in MPM.
We genotyped 199 MPM patients for ten polymorphisms: rs243865, rs243849 and rs7201, in rs17576, rs17577, rs20544, and rs2250889 in ; and rs1042703, rs1042704, and rs743257 in . We determined the influence on survival using Cox regression.
Carriers of polymorphic rs2250889 allele had shorter time to progression (TTP) (6.07 versus 10.03 months, HR = 2.45, 95% CI = 1.45-4.14, = 0.001) and OS (9.23 versus 19.2 months, HR = 2.39, 95% CI = 1.37-4.18, = 0.002). In contrast, carriers of at least one polymorphic rs20544 allele had longer TTP (10.93 versus 9.40 months, HR = 0.57, 95% CI = 0.38-0.86 = 0.007) and OS (20.67 versus 13.50 months, HR = 0.56, 95% CI = 0.37-0.85, = 0.007). rs1042703 was associated with nominally shorter TTP (8.7 versus 9.27 months, HR = 2.09, 95% CI = 1.06-4.12, = 0.032).
Selected SNPs were associated with survival and could be used as potential genetic biomarkers in MPM.
恶性胸膜间皮瘤（MPM）是一种罕见疾病，总体生存率（OS）相对较短。金属蛋白酶（MMPs）对肿瘤的进展、侵袭、转移形成和细胞凋亡有广泛的生物学影响。MMP 的表达与 MPM 患者的生存相关。我们的目的是评估基因的遗传多态性是否也可以作为 MPM 的预后生物标志物。
我们对 199 名 MPM 患者进行了 10 个多态性的基因分型：rs243865、rs243849 和 rs7201 在 MMP1 中；rs17576、rs17577、rs20544 和 rs2250889 在 MMP3 中；以及 rs1042703、rs1042704 和 rs743257 在 TIMP1 中。我们使用 Cox 回归分析来确定对生存的影响。
携带 MMP1 rs2250889 等位基因的患者进展时间（TTP）更短（6.07 个月 vs 10.03 个月，HR=2.45，95%CI=1.45-4.14，=0.001）和总生存期（OS）更短（9.23 个月 vs 19.2 个月，HR=2.39，95%CI=1.37-4.18，=0.002）。相比之下，至少携带一个 MMP3 rs20544 等位基因的患者 TTP 更长（10.93 个月 vs 9.40 个月，HR=0.57，95%CI=0.38-0.86，=0.007）和 OS 更长（20.67 个月 vs 13.50 个月，HR=0.56，95%CI=0.37-0.85，=0.007）。rs1042703 与 TTP 短（8.7 个月 vs 9.27 个月，HR=2.09，95%CI=1.06-4.12，=0.032）有显著相关性。
所选 SNP 与生存相关，可作为 MPM 的潜在遗传生物标志物。
