發(fā)布時(shí)間：2018-02-11 20:18

  本文關(guān)鍵詞： microRNA 血清 前列腺癌 標(biāo)記物 診斷　出處：《第二軍醫(yī)大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：目的:通過(guò)檢測(cè)血液中micro RNA的穩(wěn)定表達(dá),證明部分在血液中差異性表達(dá)的micro RNA可以作為前列腺癌的血液診斷分子標(biāo)志物;通過(guò)血液中穩(wěn)定差異性表達(dá)的micro RNA聯(lián)合目前臨床患者基本信息數(shù)據(jù)(年齡、前列腺體積、PSA等),探索出micro RNA聯(lián)合臨床指標(biāo)的模型協(xié)同診斷前列腺癌的新方法,以幫助臨床醫(yī)師診斷和鑒別前列腺癌與前列腺其他疾病。方法:(1)使用72例臨床血漿樣本,運(yùn)用高通量micro RNA芯片的表達(dá)分析篩選技術(shù),篩選出在前列腺癌患者、前列腺增生患者和健康對(duì)照者中穩(wěn)定差異性表達(dá)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探針的q RT-PCR方法檢測(cè)血清中的micro RNA的表達(dá)情況,運(yùn)用AUC-ROC統(tǒng)計(jì)學(xué)方法檢測(cè)入組micro RNA的診斷效能,用以驗(yàn)證芯片篩選結(jié)果在臨床的診斷價(jià)值。并運(yùn)用統(tǒng)計(jì)方法聯(lián)合PSA升高患者的前列腺體積和PSA值、f/t等,建立診斷前列腺癌的logistics回歸方程,探尋出最優(yōu)的新型診斷前列腺癌的方法,并以Panel模型在多中心血清中驗(yàn)證其診斷效能。實(shí)驗(yàn)中所用臨床血液樣本均為取樣前未經(jīng)任何前列腺疾病相關(guān)治療的患者樣本。結(jié)果:通過(guò)72例血漿樣本的高通量micro RNA芯片,篩選出15個(gè)在前列腺癌與前列腺穿刺陰性及正常人中差異性表達(dá)的micro RNA。在155例血清樣本的驗(yàn)證中,發(fā)現(xiàn)hsa-miR-365、hsa-miR-4286、hsa-miR-424、hsa-miR-27a和hsa-miR-29b等5個(gè)在PSA升高患者中差異性表達(dá)的micro RNA,具有潛在診斷價(jià)值。聯(lián)合臨床指標(biāo)計(jì)算Logistics回歸方程,得到以PSA、前列腺體積、miR-4286、miR-27a和miR-29b等5個(gè)參數(shù)組成的模型,繪制聯(lián)合診斷模型的ROC,其AUC高達(dá)0.892(95%CI:0.832 0.937),敏感性78.95%,特異性92.21%,具有良好的診斷價(jià)值,并在100例多中心血清樣本中得到了良好的驗(yàn)證。結(jié)論:miR-4286、miR-27a和miR-29b是良好的診斷前列腺癌的新型分子標(biāo)記物,具有潛在的臨床應(yīng)用價(jià)值。聯(lián)合PSA和前列腺體積等臨床指標(biāo),擁有更佳的診斷效能。
[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.
【學(xué)位授予單位】：第二軍醫(yī)大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R737.25

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本文編號(hào)：1503915