本文選題：膀胱癌　切入點：lncRNAs　出處：《山東大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：目的:越來越多的證據(jù)表明lncRNAs在腫瘤的發(fā)生發(fā)展中起著非常重要的作用。通過檢測lncRNAs在膀胱癌組織及血清中的表達水平,確定表達差異有統(tǒng)計學(xué)意義的lncRNAs,建立膀胱癌血清lncRNAs診斷模型。并進一步評價該模型對膀胱癌的診斷價值及與膀胱癌復(fù)發(fā)的關(guān)系。方法:1.通過檢索文獻獲得與膀胱癌相關(guān)的差異表達的lncRNAs作為候選lncRNAs。2.通過實時熒光定量PCR(qRT-PCR)檢測候選lncRNAs在80例膀胱癌組織及相對應(yīng)的癌旁正常組織中的表達水平,經(jīng)數(shù)據(jù)分析篩選出在膀胱癌組織和癌旁正常組織中差異表達的lncRNAs并進一步確證。3.在training階段,上述初步篩選出的lncRNAs繼續(xù)在52例健康對照者、68例良性對照者及120例膀胱癌患者的血清中通過qRT-PCR進行檢測。篩選出在膀胱癌組和健康對照組以及膀胱癌組和良性對照組之間均呈差異表達的lncRNAs。將差異表達有統(tǒng)計學(xué)意義的lncRNAs代入logistic多元回歸方程,建立膀胱癌血清lncRNA診斷模型用以區(qū)分膀胱癌組和對照組。同時用Pearson相關(guān)分析分析差異表達的lncRNAs在膀胱癌組織和相對應(yīng)的血清標(biāo)本中表達量的相關(guān)性。4.在validation階段,差異表達的lncRNAs在另外48例健康對照者、52例良性對照者以及100例膀胱癌患者血清中進一步驗證,并評估膀胱癌血清中建立的lncRNA診斷模型對膀胱癌的診斷效能。同時獲取這100名對照者和100名膀胱癌患者的尿液標(biāo)本,進行尿液脫落細胞學(xué)檢查并與診斷模型的診斷效能進行對比。5.跟蹤隨訪validation階段100名膀胱癌患者包括61名非肌層浸潤性膀胱癌患者和39名肌層浸潤性膀胱癌患者,分析差異表達的lncRNAs與膀胱癌復(fù)發(fā)的關(guān)系。通過Kaplan-Meier軟件和Cox比例風(fēng)險回歸模型分別對浸潤性膀胱癌和非浸潤性膀胱癌患者進行生存曲線分析和監(jiān)測復(fù)發(fā)的獨立預(yù)后因素的分析。結(jié)果:1.在13個候選lncRNAs分子中有11個lncRNAs分子在膀胱癌組織和癌旁組織之間呈現(xiàn)差異表達(p0.01)。2.在training階段,3個lncRNAs分子在膀胱癌和健康對照組及膀胱癌和良性對照組之間均呈現(xiàn)差異表達。MEG3表達量下降,MALAT1和SNHG16表達量升高(均p0.01)。MEG3、SNHG16和MALAT1的受試者工作曲線下面積(AUC)分別為 0.798、0.687 和 0.640。由 MEG3、SNHG16 和 MALAT1 組成的血清 lncRNA膀胱癌診斷模型的AUC為0.865(95%CI=0.815-0.905;靈敏度為71.7%,特異度為85.8%)。同時Pearson相關(guān)分析顯示MEG3、SNHG16和MALAT1在膀胱組織及相對應(yīng)的血清中的表達量呈較好的相關(guān)性,MEG3(r = 0.629,p ＜ 0.05),SNHG16(r = 0.556,尸0.05)和 MALAT1(r = 0.401,p0.05)。3.在validation階段,MEG3、SNHG16和MALAT1在膀胱癌和健康對照組及膀胱癌和良性對照組之間同樣呈現(xiàn)差異表達(均p0.01)。膀腕癌血清lncRNA診斷模型的AUC=0.828(95%CI= 0.768-0.877;靈敏度=82.0%,特異度=73.0%)。該模型對Ta、T1和T2-T4期膀胱癌的診斷效能分別為0.778、0.805和0.880,高于尿液脫落細胞學(xué)相對應(yīng)的0.548、0.604和0.682(p0.01)。4.經(jīng)Kaplan-Meier分析發(fā)現(xiàn),MG3表達水平低的非肌層浸潤性膀胱癌患者的無復(fù)發(fā)生存率顯著低于MEG3表達水平高的非肌層浸潤性膀胱癌患者(p=0.028)。經(jīng)Cox比例風(fēng)險回歸分析發(fā)現(xiàn),MEG3(p = 0.046)和臨床病理分期(T)(p = 0.041)是非浸潤性膀胱癌患者監(jiān)測復(fù)發(fā)的獨立預(yù)測指標(biāo)。在肌層浸潤性膀胱癌組未發(fā)現(xiàn)與膀胱癌患者復(fù)發(fā)有關(guān)的獨立預(yù)后指標(biāo)。結(jié)論:1.血清MEG3、SNHG16和MALAT1具有較高的膀胱癌診斷價值。2.血清lncRNA膀胱癌診斷模型可以輔助膀胱癌診斷特別是對于早期膀胱癌的診斷具有重要意義。3.血清中的MEG3可以作為非肌層浸潤性膀胱癌患者的復(fù)發(fā)監(jiān)測的獨立預(yù)后指標(biāo)。
[Abstract]:Objective: there is growing evidence that lncRNAs in tumor development plays a very important role. Through the detection of lncRNAs in bladder cancer tissues and the expression levels of serum, determine the expression difference was statistically significant lncRNAs, the establishment of serum lncRNAs in the diagnosis of bladder cancer and to further evaluate the value model. The model for bladder cancer diagnosis and the relationship with the recurrence of bladder cancer. Methods: 1. through literature retrieval obtained differences associated with bladder cancer the expression of lncRNAs as a candidate of lncRNAs.2. by real-time fluorescence quantitative PCR (qRT-PCR) to detect the expression level of candidate lncRNAs in cancer and the corresponding 80 cases of bladder cancer tissue and adjacent normal tissues, the data analysis showed that in the bladder cancer tissues and normal tissues in the differential expression of lncRNAs and.3. was further confirmed at the training stage, the preliminary selection of lncRNAs in 52 cases of healthy controls , were measured by qRT-PCR in serum of 68 cases of benign controls and 120 cases of bladder cancer patients. Screened in bladder cancer group and healthy control group and between bladder cancer group and benign control group showed the expression of lncRNAs. in the differential expression was statistically significant lncRNAs by logistic multiple regression equation was used to distinguish between bladder cancer group and control group to establish bladder cancer model. The diagnosis of serum lncRNA expression of.4. in validation stage lncRNAs correlation and Pearson correlation analysis of differential expression analysis in bladder cancer tissues and corresponding serum samples, the differential expression of lncRNAs in 48 healthy subjects, 52 patients with benign controls and 100 cases of bladder cancer in the serum of patients with further verification, and to evaluate the diagnostic efficacy of lncRNA diagnosis model of bladder cancer in serum of bladder cancer. At the same time get the 100 control subjects and 100 patients of bladder Cancer patients urine samples, urine cytology and diagnostic efficiency and diagnosis model compared to.5. followed validation stage 100 patients with bladder cancer including 61 non muscle invasive bladder cancer and 39 patients with muscle invasive bladder cancer patients, the relationship between lncRNAs and recurrence of bladder cancer differentially expressed. Through the analysis of Kaplan-Meier software and Cox proportional hazards regression model of invasive bladder cancer and non independent prognostic factors of invasive bladder cancer patients were survival curve analysis and monitoring of recurrence. Results: 1. in 13 candidate lncRNAs molecules between 11 molecules of lncRNAs in bladder cancer tissue and paracancerous tissue showed differential expression (P0.01).2. in training phase, 3 lncRNAs molecules decreased in bladder cancer and healthy controls showed the difference between bladder cancer and benign group and control group the expression of.MEG3, MALA The T1 and SNHG16 level (P0.01).MEG3, SNHG16 and MALAT1 receiver operating curve area under the curve (AUC) were 0.798,0.687 and 0.640. by MEG3 model, the diagnosis of bladder cancer serum lncRNA SNHG16 and MALAT1 AUC composed of 0.865 (95%CI=0.815-0.905; the sensitivity was 71.7%, specificity was 85.8% and Pearson). Correlation analysis showed that MEG3, there was a good correlation between the expression of SNHG16 and MALAT1 in serum and the corresponding bladder tissues, MEG3 (r = 0.629, P < 0.05), SNHG16 (r = 0.556, P 0.05) and MALAT1 (r = 0.401, P0.05) in.3. validation MEG3, SNHG16 and MALAT1 stage. In bladder cancer and healthy control group and between bladder cancer and benign control group also showed differential expression (P0.01). Serum lncRNA in the diagnosis of bladder cancer model of wrist AUC=0.828 (95%CI= 0.768-0.877 =82.0% =73.0%; sensitivity, specificity). The model of Ta, T1 and T2-T4 in bladder cancer The diagnostic efficiency of 0.778,0.805 and 0.880 respectively, higher than the corresponding urine cytology and 0.682 0.548,0.604 (P0.01).4. by Kaplan-Meier analysis, MG3 expression level is low in non muscle invasive bladder cancer were recurrence free survival rate was significantly lower than that of MEG3 expressed high levels of non muscle invasive bladder cancer patients (p=0.028) the Cox regression analysis found that MEG3 (P = 0.046) and clinical staging (T) (P = 0.041) were independent predictors of non invasive bladder cancer recurrence. Patients with invasive bladder cancer group in the muscle layer independent prognostic indicators related to recurrence of bladder cancer patients were found. Conclusion: 1. serum MEG3, serum lncRNA can model diagnosis bladder cancer bladder cancer diagnosis value of.2. SNHG16 and MALAT1 has high diagnosis of bladder cancer particularly important.3. serum MEG3 for early diagnosis of bladder cancer An independent prognostic indicator for patients with non muscular invasive bladder cancer.

【學(xué)位授予單位】：山東大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R737.14

【相似文獻】

相關(guān)期刊論文 前4條

1 李琪兒;葉國良;郭俊明;;lncRNA:腫瘤分子診斷中的一顆新星[J];中國生物化學(xué)與分子生物學(xué)報;2014年03期

2 郭秀全;藍天;王養(yǎng)民;;LncRNA在前列腺癌中的研究進展[J];中華男科學(xué)雜志;2013年09期

3 張傳壽;林秋雄;朱杰寧;鄒笑;梁業(yè)由;鄧春玉;符永恒;譚虹虹;張斌;單志新;;糖尿病性心肌纖維化中上調(diào)表達長鏈非編碼RNA(lncRNA)的鑒定[J];熱帶醫(yī)學(xué)雜志;2014年01期

4 涂超峰;武明花;李桂源;;lncRNA與miRNA相互調(diào)控作用及其與腫瘤的關(guān)系[J];中國生物化學(xué)與分子生物學(xué)報;2013年11期

相關(guān)會議論文 前3條

1 馮丹;牛勇敢;;LncRNA與腦卒中的研究分析[A];第一次全國中西醫(yī)結(jié)合檢驗醫(yī)學(xué)學(xué)術(shù)會議暨中國中西醫(yī)結(jié)合學(xué)會檢驗醫(yī)學(xué)專業(yè)委員會成立大會論文匯編[C];2014年

2 李夏君;楊淼;劉冉;尹立紅;;淮安食管癌與癌旁組織中差異表達LncRNA的初步分析[A];中國毒理學(xué)會第六屆全國毒理學(xué)大會論文摘要[C];2013年

3 沈遠;付漢江;朱娟娟;劉珊珊;鐘一然;鄭曉飛;;應(yīng)用多重PCR方法進行l(wèi)ncRNA功能研究[A];中國生物化學(xué)與分子生物學(xué)會第十一次會員代表大會暨2014年全國學(xué)術(shù)會議論文集——專題報告五[C];2014年

相關(guān)博士學(xué)位論文 前3條

1 王富博;尿液lncRNA在前列腺癌早期診斷以及新型miRNA在進展機制中的研究[D];第二軍醫(yī)大學(xué);2016年

2 陳升東;精神分裂癥外周血單核細胞中差異性表達lncRNA的臨床和實驗研究[D];第二軍醫(yī)大學(xué);2016年

3 劉佳;靜態(tài)牽張力作用下健康和牙周病微環(huán)境來源PDLSCs生物學(xué)功能及LncRNA表達譜的研究[D];第四軍醫(yī)大學(xué);2016年

相關(guān)碩士學(xué)位論文 前10條

1 周明;人胰腺癌吉西他濱耐藥細胞株中l(wèi)ncRNA表達譜初步篩選及研究[D];蘇州大學(xué);2015年

2 郝超;LncRNA在前列腺增生性炎性萎縮向前列腺癌惡性轉(zhuǎn)化過程中差異表達的初步研究[D];南昌大學(xué)醫(yī)學(xué)院;2015年

3 金雯;基于結(jié)構(gòu)的植物lncRNA相互作用研究[D];吉林大學(xué);2016年

4 孫影;基于miRNA的lncRNA和mRNA的調(diào)控網(wǎng)絡(luò)[D];吉林大學(xué);2016年

5 李凌雪;lncRNA參與幽門螺桿菌感染相關(guān)胃癌的功能及機制研究[D];北京協(xié)和醫(yī)學(xué)院;2016年

6 劉紅梅;GMA誘導(dǎo)的16HBE惡性轉(zhuǎn)化細胞相關(guān)差異LncRNA篩選及其研究[D];中國疾病預(yù)防控制中心;2016年

7 趙寧;產(chǎn)腸毒素性大腸桿菌感染小鼠致腹瀉LncRNA表達譜的構(gòu)建[D];寧夏大學(xué);2016年

8 陳牡丹;LncRNA在肝硬化進程中的差異表達[D];福建醫(yī)科大學(xué);2016年

9 廖武;長鏈非編碼RNA(lncRNA)在穩(wěn)定性心絞痛中的表達譜分析[D];新疆醫(yī)科大學(xué);2017年

10 段偉麗;膀胱癌血清lncRNA診斷模型的建立及其對膀胱癌復(fù)發(fā)監(jiān)測的臨床意義[D];山東大學(xué);2017年

，

本文編號：1591875