本文選題：原發(fā)性肝癌 + 微小RNA　； 參考：《天津醫(yī)科大學(xué)》2015年碩士論文

【摘要】：目的循環(huán)腫瘤標(biāo)志物有助于診斷早期原發(fā)性肝細(xì)胞癌(hepatocellular carcinoma,HCC),然而目前輔助臨床診斷的HCC標(biāo)志物并不令人滿意,主要問題在于其準(zhǔn)確性、靈敏性和特異性均較低。循環(huán)微小RNA(microRNAs,miRNAs)的研究方向帶來了新的思路。本研究探討mi R-125b、miR-223、miR-27a和mi R-26a作為HCC血清標(biāo)志物的可能性和臨床價值。通過聯(lián)合檢測來提高篩查診斷早期HCC的準(zhǔn)確性、靈敏性和特異性。方法選取天津醫(yī)科大學(xué)腫瘤醫(yī)院90例原發(fā)性乙肝肝炎病毒(hepatitis B virus,HBV)相關(guān)的HCC患者為實驗組(HCC組),30例健康志愿者(健康對照組)和30例HBV患者(HBV組)為對照組。分別采用巴塞羅那分期(Barcelona Clinic Liver Cancer,BCLC)和TNM(Tumor-node-etastasis)分期系統(tǒng)定義早期HCC患者。通過實時熒光定量PCR(quantitative real-time polymerase chain reaction,qRT-PCR)檢測各組的血清miR-125b、miR-223、mi R-27a和miR-26a,并采用2-△△Ct進(jìn)行mi RNAs相對表達(dá)量分析。利用R 3.1軟件完成統(tǒng)計分析。單一指標(biāo)篩查之后,通過logistic回歸模型實現(xiàn)多指標(biāo)聯(lián)合診斷HCC和早期HCC,并應(yīng)用于健康對照組、HBV組,以及非癌癥組(健康對照組+HBV組)中進(jìn)行受試者工作曲線(receiver operating characteristic curve,ROC)分析,確定各指標(biāo)診斷的靈敏性和特異性,并由Bootstrap確定構(gòu)建模型的穩(wěn)定性。結(jié)果1.分別與健康對照組和HBV組相比,HCC患者血清中的miR-125b、miR-223、miR-27a和miR-26a相對表達(dá)水平降低(P0.0001)。2.以非癌癥組為對照,單一mi RNA篩查診斷HCC效能最好的是miR-27a,AUC為0.849,靈敏性為73.0%,特異性為85.0%;聯(lián)合四種miRNAs診斷的AUC提高為0.870,靈敏性提高為79.8%,特異性為81.7%。以健康對照組為對照,單一miRNA篩查診斷HCC效能最好的是miR-27a,AUC為0.930,靈敏性為94.0%,特異性為77.0%;聯(lián)合四種miRNAs診斷的AUC提高為0.970,靈敏性為94.0%,特異性提高為90.0%。以HBV組為對照,單一miRNA篩查診斷HCC效能最好的是miR-223,AUC為0.826,靈敏性為73.0%,特異性為83.3%;聯(lián)合四種miRNAs診斷的AUC提高為0.833,靈敏性提高為82.0%,特異性為76.7%。3.基于BCLC分期,以非癌癥組為對照,單一miRNA篩查診斷早期HCC效能最好的是miR-223,AUC為0.793,靈敏性為70.4%,特異性為81.7%;聯(lián)合四種miRNAs診斷的AUC提高為0.843,靈敏性提高為81.5%,特異性為75.0%。以健康對照組為對照,單一miRNA篩查診斷早期HCC效能最好的是miR-27a,AUC為0.920,靈敏性為81.0%,特異性為90.0%;聯(lián)合四種miRNAs診斷的AUC提高為0.960,靈敏性為80.0%,特異性提高為100.0%。以HBV組為對照,單一miRNA篩查診斷早期HCC效能最好的是miR-223,AUC為0.809,靈敏性為74.1%,特異性為83.3%;聯(lián)合四種miRNAs診斷的AUC提高為0.812,靈敏性為70.4%,特異性為83.3%。4.基于TNM分期,以非癌癥組或HBV組為對照,單一和聯(lián)合四種miRNAs篩查診斷早期HCC效能均不令人滿意。以健康對照組為對照,單一miRNA篩查診斷早期HCC效能最好的是miR-27a,AUC為0.860,靈敏性為92.3%,特異性為73.3%;聯(lián)合四種miRNAs診斷的AUC提高為0.920,靈敏性為92.3%,特異性提高為83.3%。5.經(jīng)統(tǒng)計分析驗證,構(gòu)建的診斷模型和風(fēng)險分析模型穩(wěn)定。這四種miRNAs的相對表達(dá)量越低,患HCC風(fēng)險越大。結(jié)論1.與對照組相比,本研究確定了在HCC患者血清中的miR-125b、miR-223、miR-27a、mi R-26a相對表達(dá)水平顯著降低。2.四種miRNAs聯(lián)合檢測能夠顯著地提高診斷HCC和早期HCC的靈敏性、特異性和準(zhǔn)確性。3.四種miRNAs相對表達(dá)量與非癌癥人群患HCC風(fēng)險呈負(fù)相關(guān)。有望用于臨床,成為新的診斷早期HCC的血清標(biāo)志物。
[Abstract]:Objective circulating tumor markers are helpful for the diagnosis of hepatocellular carcinoma (HCC) in the early stage. However, the HCC marker for auxiliary clinical diagnosis is not satisfactory, the main problem is its accuracy, sensitivity and specificity are low. The research direction of microRNAs (miRNAs) has brought new ideas. The possibility and clinical value of MI R-125b, miR-223, miR-27a and MI R-26a as HCC serum markers are studied to improve the accuracy, sensitivity and specificity of early HCC in screening and diagnosis by joint detection. Methods 90 cases of primary hepatitis B hepatitis B virus (hepatitis B virus, HBV) in the Cancer Hospital of Medical University Of Tianjin are selected. In the experimental group (group HCC), 30 healthy volunteers (healthy control group) and 30 patients with HBV (group HBV) were used as the control group. The early HCC patients were defined by the Barcelona staging (Barcelona Clinic Liver Cancer, BCLC) and TNM (Tumor-node-etastasis) staging system respectively. N, qRT-PCR) detected the serum miR-125b, miR-223, MI R-27a and miR-26a, and analyzed the relative expression of MI RNAs by 2- Delta Delta Ct. Using R 3.1 software to complete the statistical analysis. After the single index screening, the multiple index joint diagnosis and early childhood were implemented by the single index screening model, and applied to the health control group, the group, and non cancer. The patient's work curve (receiver operating characteristic curve, ROC) was analyzed in the +HBV group of the healthy control group, and the sensitivity and specificity of the diagnosis were determined, and the stability of the model was determined by Bootstrap. Results 1. compared with the healthy control group and the HBV group, miR-125b, miR-223, miR-27a in the serum of the HCC patients, respectively. MiR-26a relative expression level decreased (P0.0001).2. in non cancer group, and single mi RNA screening was best for miR-27a, AUC was 0.849, sensitivity was 73%, specificity was 85%, AUC increased by 0.870, sensitivity increased 79.8%, specificity was 81.7%. in healthy control group as control, single miRNA. The best screening diagnostic HCC was miR-27a, AUC was 0.930, the sensitivity was 94%, the specificity was 77%, the AUC of the combined four miRNAs diagnosis was 0.970, the sensitivity was 94%, the specificity was improved to the HBV group, and the single miRNA screening was the best for miR-223, AUC 0.826, the sensitivity 73% and the specificity 83.3%. The AUC improvement of the four miRNAs diagnoses was 0.833, the sensitivity increased 82%, the specificity was 76.7%.3. based on the BCLC staging and the non cancer group as the control. The best HCC efficacy was miR-223, AUC was 0.793, the sensitivity was 70.4%, the specificity was 81.7%, four miRNAs diagnostic AUC increased 0.843, and the sensitivity increased 81. .5%, the specificity was 75.0%. in the healthy control group. The best diagnosis of early HCC by single miRNA screening was miR-27a, AUC was 0.920, the sensitivity was 81%, and the specificity was 90%; the AUC of the combined four miRNAs diagnoses was 0.960, the sensitivity was 80%, the specificity was increased to 100.0%. in HBV group, and the single miRNA screening was used to diagnose the early HCC effect. The best is miR-223, AUC is 0.809, the sensitivity is 74.1%, the specificity is 83.3%; the AUC of the combined four miRNAs diagnosis is 0.812, the sensitivity is 70.4%, the specificity is 83.3%.4. based on the TNM staging, the non cancer group or the HBV group as the control, the single and combined four miRNAs screening diagnosis early HCC efficacy is not satisfactory. In the health control group, the control group is not satisfactory. The best diagnosis of early HCC was miR-27a, AUC was 0.860, the sensitivity was 0.860, the sensitivity was 92.3%, the specificity was 73.3%, the AUC of the combined four miRNAs diagnosis was 0.920, the sensitivity was 92.3%, the specificity was improved by 83.3%.5. by statistical analysis, and the constructed diagnostic model and the risk analysis model were stable. The relative of the four miRNAs The lower the amount of expression, the greater the risk of developing HCC. Conclusion 1. compared with the control group, the present study determined that the relative expression level of miR-125b, miR-223, miR-27a, MI R-26a in the serum of HCC patients was significantly lower than that of the.2. and four miRNAs combinations, which could significantly improve the sensitivity, specificity and accuracy of the four kinds of.3.. There is a negative correlation between the amount and the risk of HCC in non cancer patients. It is expected to be used as a new serum marker for early diagnosis of HCC.

【學(xué)位授予單位】：天津醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2015
【分類號】：R735.7

【相似文獻(xiàn)】

相關(guān)期刊論文 前10條

1 ;第六屆全國聽力與耳聾基礎(chǔ)和臨床新進(jìn)展研討會暨第十六屆全國0～6歲兒童聽力篩查診斷和康復(fù)培訓(xùn)班通知[J];中國耳鼻咽喉頭頸外科;2010年05期

2 ;第六屆全國聽力與耳聾基礎(chǔ)和臨床新進(jìn)展研討會暨第十六屆全國0～6歲兒童聽力篩查診斷和康復(fù)培訓(xùn)班通知[J];中國醫(yī)學(xué)文摘(耳鼻咽喉科學(xué));2010年03期

3 ;第六屆全國聽力與耳聾基礎(chǔ)和臨床新進(jìn)展研討會暨第十六屆全國0～6歲兒童聽力篩查診斷和康復(fù)培訓(xùn)班通知[J];中國耳鼻咽喉頭頸外科;2010年04期

4 高嶺;申改青;張松華;;尿液氣相色譜-質(zhì)譜分析法篩查診斷代謝缺陷病的臨床研究[J];現(xiàn)代中西醫(yī)結(jié)合雜志;2008年01期

5 林果為;王小欽;;提高臨床貧血篩查診斷水平的若干建議[J];診斷學(xué)理論與實踐;2010年03期

6 楊揚(yáng);張杰;劉衛(wèi)一;張亞梅;;學(xué)齡兒童阻塞性睡眠呼吸暫停低通氣綜合征篩查診斷指標(biāo)探討[J];中國耳鼻咽喉頭頸外科;2010年10期

7 黃麗輝;葉勝難;;“暢聽未來”——第九屆全國0～6歲兒童聽力篩查診斷培訓(xùn)班圓滿結(jié)束[J];中國醫(yī)學(xué)文摘(耳鼻咽喉科學(xué));2007年05期

8 ;第五屆聽力與耳聾基礎(chǔ)和臨床新進(jìn)展學(xué)習(xí)班暨第十一屆全國0～6歲兒童聽力篩查診斷培訓(xùn)班通知[J];聽力學(xué)及言語疾病雜志;2008年06期

9 亓貝爾;黃麗輝;;“暢聽未來”——第十二屆全國0～6歲兒童聽力篩查診斷培訓(xùn)班圓滿結(jié)束[J];中國醫(yī)學(xué)文摘(耳鼻咽喉科學(xué));2009年03期

10 程曉華;;第十五屆全國0～6歲兒童聽力篩查診斷培訓(xùn)班圓滿結(jié)束[J];中國醫(yī)學(xué)文摘(耳鼻咽喉科學(xué));2010年03期

相關(guān)重要報紙文章 前2條

1 董良軍;市政府采取緊急措施確保嬰幼兒篩查診斷平穩(wěn)有序[N];安康日報;2008年

2 記者 葉青 通訊員 開蘿人;廣州兩企業(yè)榜上有名[N];廣東科技報;2009年

相關(guān)碩士學(xué)位論文 前2條

1 左鐸;血清四種microRNAs聯(lián)合診斷早期原發(fā)性肝細(xì)胞肝癌的初步分析[D];天津醫(yī)科大學(xué);2015年

2 張佰爽;血漿醛固酮/腎素活性比值在原發(fā)性醛固酮增多癥篩查診斷中的臨床應(yīng)用[D];大連醫(yī)科大學(xué);2014年

，

本文編號：1857366