三種微小RNA作為膠質(zhì)瘤診斷潛在生物標(biāo)志物的研究
發(fā)布時(shí)間:2018-05-17 21:26
本文選題:miRNA + 膠質(zhì)瘤; 參考:《南京醫(yī)科大學(xué)》2017年博士論文
【摘要】:目的:血液中的生物標(biāo)志物用來(lái)幫助診斷膠質(zhì)瘤越來(lái)越受到重視,外周血液中的微小核糖核酸(microRNA;miRNA)與惡性腫瘤的相關(guān)性已得到認(rèn)可。我們通過(guò)膠質(zhì)瘤病人血液標(biāo)本中miRNA的不同表達(dá)的差異,來(lái)確定miRNA對(duì)膠質(zhì)瘤的診斷性能。方法:將共47位膠質(zhì)瘤病人及45位健康志愿者作為研究對(duì)象,膠質(zhì)瘤病人納入膠質(zhì)瘤研究組,健康自愿者為健康對(duì)照組。Trizol法分離提取研究對(duì)象的總RNA,miRNA微陣列獲取miRNA差異表達(dá)族譜。定量反轉(zhuǎn)錄聚合酶鏈?zhǔn)椒磻?yīng)(quantitative Reverse Transcription PCR,qRT-PCR)驗(yàn)證選定的三種 miRNA的表達(dá),建立logistic回歸分析,產(chǎn)生的受試者工作特征曲線(receiver operating characteristic curves;ROC)和曲線下面積(the area under the ROC curve;AUC)用來(lái)評(píng)價(jià)這三種微RNA作為膠質(zhì)瘤生物標(biāo)志物的診斷性能。結(jié)果:微陣列數(shù)據(jù)顯示膠質(zhì)瘤病人血液中有13種miRNA表達(dá)異常,最為顯著的是miRNA-17,miRNA-130a,和miRNA-10b的表達(dá)顯著高于健康對(duì)照組(P0.01),進(jìn)一步研究發(fā)現(xiàn),miRNA-17,miRNA-130a 和 miRNA-10b 的 AUC(95%CI)分別為 0.78(0.69-0.86),0.72(0.62-0.81),0.72(0.62-0.80)。多元logistic回歸篩選提示膠質(zhì)瘤發(fā)病與年齡及性別無(wú)關(guān),而與miRNA-17,miRNA-130a和miRNA-10b表達(dá)成相關(guān)性。多元logistic回歸預(yù)測(cè)模型得出的miRNA 回歸方程=-5.0+0.55*miR-17+0.40*miR-130a +0.20*miR-10b,此模型方程具有優(yōu)異的診斷性能:AUC為0.87(0.78-0.93),敏感性為72.3%,特異性為85.1%。結(jié)論:上述三種miRNA在膠質(zhì)瘤病人中顯著增高,因此是一種敏感且可靠的新的膠質(zhì)瘤診斷的生物標(biāo)志物,且三種特定的miRNA聯(lián)合檢測(cè)、分析具有更高的診斷性能。
[Abstract]:Objective: more and more attention has been paid to the use of biomarkers in blood for the diagnosis of gliomas. The relationship between microRNAs in peripheral blood and malignant tumors has been recognized. The differential expression of miRNA in blood samples of glioma patients was used to determine the diagnostic performance of miRNA for glioma. Methods: a total of 47 glioma patients and 45 healthy volunteers were included in the glioma study group. The miRNA differentially expressed genealogy was obtained from the total RNA-miRNA microarray extracted from healthy volunteers by Trizol method. Quantitative reverse transcriptase polymerase chain reaction (Reverse Transcription) quantitative Reverse Transcription qRT-PCR was used to verify the expression of three kinds of miRNA, and logistic regression analysis was established. The receiver operating characteristic curvess-ROC and the area under the curve were used to evaluate the diagnostic performance of these three microRNA as biomarkers of glioma. Results: microarray data showed that there were 13 abnormal miRNA expressions in the blood of glioma patients, the most significant being miRNA-17 miRNA-130 a, and the expression of miRNA-17 miRNA-130 a and miRNA-10b were significantly higher than that of the healthy control group (P0.01a). Further studies showed that the expression of miRNA-17miRNA-130a and miRNA-10b were 0.780.69-0.860.7620.62-0.81a and 0.62-0.80, respectively. Multiple logistic regression analysis showed that glioma had no relationship with age and sex, but was correlated with miRNA-17 miRNA-130a and miRNA-10b expression. The miRNA regression equation obtained from the multivariate logistic regression prediction model was -5.0 0.55*miR-17 0.40*miR-130a 0.20 miR-10b. The model equation had excellent diagnostic performance. The sensitivity was 72.3% and the specificity was 85.1%. Conclusion: these three kinds of miRNA are significantly increased in glioma patients, so they are a sensitive and reliable biomarker for the diagnosis of glioma, and the combined detection of three specific miRNA has higher diagnostic performance.
【學(xué)位授予單位】:南京醫(yī)科大學(xué)
【學(xué)位級(jí)別】:博士
【學(xué)位授予年份】:2017
【分類號(hào)】:R739.41
【參考文獻(xiàn)】
相關(guān)期刊論文 前1條
1 Chin-Ann J Ong;Pierre Lao-Sirieix;Rebecca C Fitzgerald;;Biomarkers in Barrett's esophagus and esophageal adenocarcinoma:Predictors of progression and prognosis[J];World Journal of Gastroenterology;2010年45期
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