外周血中microRNA在诊断前列腺癌中的作用研究

发布时间：2018-02-11 20:18

本文关键词： microRNA 血清前列腺癌标记物诊断　出处：《第二军医大学》2017年硕士论文　论文类型：学位论文

【摘要】：目的:通过检测血液中micro RNA的稳定表达,证明部分在血液中差异性表达的micro RNA可以作为前列腺癌的血液诊断分子标志物;通过血液中稳定差异性表达的micro RNA联合目前临床患者基本信息数据(年龄、前列腺体积、PSA等),探索出micro RNA联合临床指标的模型协同诊断前列腺癌的新方法,以帮助临床医师诊断和鉴别前列腺癌与前列腺其他疾病。方法:(1)使用72例临床血浆样本,运用高通量micro RNA芯片的表达分析筛选技术,筛选出在前列腺癌患者、前列腺增生患者和健康对照者中稳定差异性表达的micro RNA。(2)收集我院前列腺增生和前列腺癌患者的血清,使用Taqman探针的q RT-PCR方法检测血清中的micro RNA的表达情况,运用AUC-ROC统计学方法检测入组micro RNA的诊断效能,用以验证芯片筛选结果在临床的诊断价值。并运用统计方法联合PSA升高患者的前列腺体积和PSA值、f/t等,建立诊断前列腺癌的logistics回归方程,探寻出最优的新型诊断前列腺癌的方法,并以Panel模型在多中心血清中验证其诊断效能。实验中所用临床血液样本均为取样前未经任何前列腺疾病相关治疗的患者样本。结果:通过72例血浆样本的高通量micro RNA芯片,筛选出15个在前列腺癌与前列腺穿刺阴性及正常人中差异性表达的micro RNA。在155例血清样本的验证中,发现hsa-miR-365、hsa-miR-4286、hsa-miR-424、hsa-miR-27a和hsa-miR-29b等5个在PSA升高患者中差异性表达的micro RNA,具有潜在诊断价值。联合临床指标计算Logistics回归方程,得到以PSA、前列腺体积、miR-4286、miR-27a和miR-29b等5个参数组成的模型,绘制联合诊断模型的ROC,其AUC高达0.892(95%CI:0.832 0.937),敏感性78.95%,特异性92.21%,具有良好的诊断价值,并在100例多中心血清样本中得到了良好的验证。结论:miR-4286、miR-27a和miR-29b是良好的诊断前列腺癌的新型分子标记物,具有潜在的临床应用价值。联合PSA和前列腺体积等临床指标,拥有更佳的诊断效能。
[Abstract]:Objective: to detect the stable expression of micro RNA in blood, and to prove that micro RNA, which is expressed differently in blood, can be used as a molecular marker for blood diagnosis of prostate cancer. By using stable and differential expression of micro RNA in blood combined with basic information data of current clinical patients (age, prostate volume, PSA, etc.), a new method of co-diagnosis of prostate cancer by micro RNA combined with clinical indexes was explored. To help clinicians diagnose and differentiate prostate cancer from other diseases of the prostate. Methods Twenty two clinical plasma samples were used to screen prostate cancer patients with high throughput micro RNA microarray. Serum samples of patients with prostatic hyperplasia and prostate cancer were collected from our hospital. The expression of micro RNA in serum was detected by Q RT-PCR method with Taqman probe. The diagnostic efficacy of micro RNA was detected by AUC-ROC statistical method to verify the diagnostic value of the results of microarray screening. The prostatic volume and PSA value of the patients were increased by using the statistical method combined with PSA to increase the volume of prostate and the value of PSA / f / t, etc. To establish the logistics regression equation for the diagnosis of prostate cancer and to find out the best new method for the diagnosis of prostate cancer. Panel model was used to test its diagnostic efficacy in multi-center serum. The clinical blood samples were collected from patients without any prostatic disease-related treatment before sampling. Results: high throughput micro RNA microarray was used in 72 plasma samples. Fifteen micro RNAs, which were differentially expressed in prostate cancer and prostate puncture negative and normal subjects, were screened out in 155 serum samples. Five differentially expressed micro RNAs including hsa-miR-365hsa-miR-4286hsa-miR-424hsa-miR-27a and hsa-miR-29b were found to be of potential diagnostic value in patients with elevated PSA. A model consisting of five parameters, PSA-MIR-4286miR-27a and miR-29b, was obtained by combining clinical indexes with Logistics regression equation. The AUC of the joint diagnostic model is as high as 0.892c95CI0.832 and 0.9377.It has a sensitivity of 78.95 and a specificity of 92.21. it has good diagnostic value. It was well verified in 100 multi-center serum samples. Conclusion: miR-4286miR-27a and miR-29b are new molecular markers for the diagnosis of prostate cancer, which have potential clinical application value, combined with PSA and prostatic volume, and so on. Better diagnostic efficacy.
【学位授予单位】：第二军医大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R737.25

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