三種微小RNA作為膠質(zhì)瘤診斷潛在生物標志物的研究
發(fā)布時間:2018-05-17 21:26
本文選題:miRNA + 膠質(zhì)瘤 ; 參考:《南京醫(yī)科大學》2017年博士論文
【摘要】:目的:血液中的生物標志物用來幫助診斷膠質(zhì)瘤越來越受到重視,外周血液中的微小核糖核酸(microRNA;miRNA)與惡性腫瘤的相關性已得到認可。我們通過膠質(zhì)瘤病人血液標本中miRNA的不同表達的差異,來確定miRNA對膠質(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照組。Trizol法分離提取研究對象的總RNA,miRNA微陣列獲取miRNA差異表達族譜。定量反轉(zhuǎn)錄聚合酶鏈式反應(quantitative Reverse Transcription PCR,qRT-PCR)驗證選定的三種 miRNA的表達,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)用來評價這三種微RNA作為膠質(zhì)瘤生物標志物的診斷性能。結果:微陣列數(shù)據(jù)顯示膠質(zhì)瘤病人血液中有13種miRNA表達異常,最為顯著的是miRNA-17,miRNA-130a,和miRNA-10b的表達顯著高于健康對照組(P0.01),進一步研究發(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)病與年齡及性別無關,而與miRNA-17,miRNA-130a和miRNA-10b表達成相關性。多元logistic回歸預測模型得出的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)瘤診斷的生物標志物,且三種特定的miRNA聯(lián)合檢測、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.
【學位授予單位】:南京醫(yī)科大學
【學位級別】:博士
【學位授予年份】:2017
【分類號】:R739.41
【參考文獻】
相關期刊論文 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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