miR-17-92 簇启动子区域的多态性与子宫内膜癌的风险和预后相关。
Polymorphisms in miR-17-92 cluster promoter region is associated with risk and prognosis of endometrial cancer.
机构信息
Department of Obstetrics and Gynaecology, The Second Affiliated Hospital of Shandong First Medical University, Tai'an, Shandong, China.
Department of Gynecological Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China.
出版信息
Medicine (Baltimore). 2024 Aug 16;103(33):e39326. doi: 10.1097/MD.0000000000039326.
Accumulating researches have reported that miR-17-92 cluster expression has strong association with tumorigenesis. In this study, we investigated the effects of 2 genetic polymorphisms in the promoter region of the miR-17-92 cluster and the risk and prognosis of endometrial cancer in northern Chinese women. Two polymorphisms (rs9588884 and rs982873) in the promoter of miR-17-92 cluster were genotyped by polymerase chain reaction and ligase detection reaction (PCR-LDR) in398 EC patients and 420 controls. The levels of miR-17-92 mRNA were investigated in 65EC tissues by real-time quantitative polymerase chain reaction (RT-qPCR). The impact of genetic features on the risk and clinical outcomes of EC was analyzed. The prognostic value of hsa-miR-17 and hsa-miR-20a in EC patients was assessed using the Kaplan-Meier plotter database. The results showed that a significant decrease in risk of EC with rs9588884 (GG vs CC: OR = 0.49, 95% CI = 0.32-0.78, P = .002; G vs C: OR = 0.75, 95% CI = 0.62-0.91, P = .005, respectively). Similarly, association was found between rs982873 and a decreased risk of EC (CC vs TT: OR = 0.53, 95% CI = 0.34-0.82, P = .004; C vs T: OR = 0.77, 95% CI = 0.63-0.94, P = .010, respectively). Moreover, survival analysis showed that the CG or GG genotype of rs9588884 may significantly increase overall survival (OS) compared with the CC genotype in the 5-year follow-up (HR = 0.49, 95% CI = 0.29-0.82 and HR = 0.36, 95% CI = 0.16-0.83, respectively). RT-qPCR results showed that the expression level of miR-17-92 mRNA in EC tissues with the rs9588884 GG genotype was significantly lower than those with the GC + CC genotype (P = .030). However, there was no significant difference in the prognosis and expression level of miR-17-92mRNA in tissues of EC patients with different genotypes of rs982873 (P = .343). In addition, analysis using Kaplan-Meier plotter database showed that high hsa-miR-20a expression was significantly correlated with poor OS in EC patients (HR = 1.63, 95% CI = 1.02-2.61, P = .039). The genetic polymorphisms rs9588884 and rs982873 in the promoter of miR-17-92 cluster decreased EC risk. Both rs9588884 and the expression level of hsa-miR-20a mRNA may be associated with its clinical outcome in EC patients.
越来越多的研究报告表明，miR-17-92 簇的表达与肿瘤发生有很强的关联。在这项研究中，我们调查了 miR-17-92 簇启动子区域中的 2 种遗传多态性与中国北方女性子宫内膜癌的发病风险和预后的关系。通过聚合酶链反应和连接酶检测反应（PCR-LDR），在 398 名 EC 患者和 420 名对照中对 miR-17-92 簇启动子中的 2 个多态性（rs9588884 和 rs982873）进行了基因分型。通过实时定量聚合酶链反应（RT-qPCR）检测了 65 个 EC 组织中 miR-17-92 mRNA 的水平。分析了遗传特征对 EC 风险和临床结局的影响。使用 Kaplan-Meier plotter 数据库评估了 hsa-miR-17 和 hsa-miR-20a 在 EC 患者中的预后价值。结果表明，rs9588884（GG 与 CC：OR=0.49，95%CI=0.32-0.78，P=0.002；G 与 C：OR=0.75，95%CI=0.62-0.91，P=0.005）的基因型与 EC 风险显著降低相关。同样，rs982873 与 EC 风险降低相关（CC 与 TT：OR=0.53，95%CI=0.34-0.82，P=0.004；C 与 T：OR=0.77，95%CI=0.63-0.94，P=0.010）。此外，生存分析表明，在 5 年随访中，rs9588884 的 CG 或 GG 基因型与 CC 基因型相比，可能显著增加总生存率（OS）（HR=0.49，95%CI=0.29-0.82 和 HR=0.36，95%CI=0.16-0.83，分别）。RT-qPCR 结果表明，rs9588884 GG 基因型 EC 组织中 miR-17-92 mRNA 的表达水平明显低于 GC+CC 基因型（P=0.030）。然而，在 rs982873 不同基因型的 EC 患者组织中，miR-17-92mRNA 的预后和表达水平无显著差异（P=0.343）。此外，使用 Kaplan-Meier plotter 数据库的分析表明，hsa-miR-20a 的高表达与 EC 患者的不良 OS 显著相关（HR=1.63，95%CI=1.02-2.61，P=0.039）。miR-17-92 簇启动子中的遗传多态性 rs9588884 和 rs982873 降低了 EC 的发病风险。rs9588884 与 hsa-miR-20a mRNA 的表达水平可能都与 EC 患者的临床结局有关。
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