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  本文選題：DNA甲基化　切入點：腎細胞癌　出處：《福建醫(yī)科大學(xué)》2014年碩士論文　論文類型：學(xué)位論文

【摘要】：目的：通過檢測腎細胞癌組織和尿液中TCF21基因甲基化情況，分析TCF21基因甲基化水平與腎細胞癌臨床特征的關(guān)系及相關(guān)性，用ROC曲線比較組織切片與尿液樣本兩種檢測手段診斷腎細胞癌的靈敏度和特異度，探討TCF21作為腎細胞癌中候選生物標志物在腎細胞癌早期診斷與預(yù)后的意義。 方法：選取腎細胞癌組織55例作為試驗組、隨機選取相應(yīng)遠離腫瘤的正常腎組織21例作為對照組，同時隨機選取腎細胞癌患者術(shù)前尿液標本33例及正常人尿液15例作為對照組。使用焦磷酸測序技術(shù)對上述樣本的TCF21基因啟動子甲基化水平進行定量檢測。運用Mann-Whitney U非參數(shù)秩和檢驗統(tǒng)計分析，，分析TCF21甲基化水平與臨床病理特征之間的關(guān)系；用Spearman分析TCF21甲基化水平與臨床病理特征之間的相關(guān)性；用受試者接收操作特征(ROC)曲線來測繪真陽性率和假陽性率，分析比較腎細胞癌組織與尿液樣本TCF21甲基化水平用于腎細胞癌診斷效價。 結(jié)果： 1.腎細胞癌組織中TCF21基因甲基化水平明顯高于癌旁正常腎組織中TCF21基因甲基化水平,二者的差異有統(tǒng)計學(xué)意義(P0.05)。腎細胞癌組織中TCF21甲基化水平與不同的年齡、吸煙史、病理分級及臨床分期有關(guān)（P＜0.05），與年齡（R=0.166，P=0.002）、吸煙史（R=0.321，P=0.017）和Fuhrman分級（R=0.271，P=0.045）呈正相關(guān)。 2.腎細胞癌尿液患者中TCF21基因甲基化水平明顯高于正常尿液樣本中TCF21基因甲基化水平,二者的差異有統(tǒng)計學(xué)意義(P0.05)；尿液樣本中TCF21甲基化水平與不同的腫瘤大小、病理分級及臨床分期有關(guān)（P＜0.05），與腫瘤大�。≧=0.622，P=0.000）、Fuhrman分級（R=0.441，P=0.010）和臨床分期（R=0.411，P=0.017）呈正相關(guān)。 3.腎細胞癌組織中TCF21甲基化水平診斷腎細胞癌的ROC曲線下面積高于尿液樣本中TCF21甲基化水平，腎細胞癌組織中TCF21甲基化水平和尿液樣本中TCF21甲基化水平檢測在診斷腎細胞癌時的ROC曲線下面積間的差異具有統(tǒng)計學(xué)意義（P＜0.05），組織切片診斷靈敏度和特異度為89%和61.9%，尿液樣本診斷靈敏度和特異度分別為79%和100%。 結(jié)論:TCF21與腎細胞癌的發(fā)生有關(guān),腎細胞癌中的TCF21甲基化水平可以作為腎細胞癌早期診斷指標。TCF21甲基化水平與腎細胞癌的發(fā)展,惡性程度和分化程度有重要的關(guān)系。尿液樣本檢測具有收集方便、無創(chuàng)性及檢測精確等優(yōu)點，尿液樣本的無創(chuàng)性高通量甲基化檢測可作為組織甲基化檢測的重要補充，可作為判斷腎細胞癌惡性程度及預(yù)后等生物學(xué)的行為的重要檢測手段。
[Abstract]:Objective: to study the relationship between methylation of TCF21 gene and clinical features of renal cell carcinoma (RCC) by detecting the methylation of TCF21 gene in renal cell carcinoma (RCC) tissues and urine. ROC curves were used to compare the sensitivity and specificity of tissue sections and urine samples in the diagnosis of renal cell carcinoma. The significance of TCF21 as a candidate biomarker in the early diagnosis and prognosis of renal cell carcinoma was discussed. Methods: 55 cases of renal cell carcinoma (RCC) were selected as experimental group and 21 cases of normal renal tissue which were away from tumor were randomly selected as control group. At the same time, 33 urine samples from patients with renal cell carcinoma and 15 normal urine samples were randomly selected as control group. The methylation level of TCF21 gene promoter was quantitatively detected by pyrosequencing technique. Mann-Whitney was used to detect the methylation level of the promoter of the TCF21 gene. U nonparametric rank sum test statistical analysis, To analyze the relationship between TCF21 methylation level and clinicopathological features; to analyze the correlation between TCF21 methylation level and clinicopathological features by Spearman; to map true positive rate and false positive rate by using receiver operating characteristics curve. To analyze and compare the TCF21 methylation level in renal cell carcinoma (RCC) tissues and urine samples for the diagnosis of renal cell carcinoma (RCC). Results:. 1. The methylation level of TCF21 gene in renal cell carcinoma tissues was significantly higher than that in adjacent normal renal tissues, and the difference was statistically significant (P 0.05). The methylation level of TCF21 in renal cell carcinoma tissues was different from that in different ages and smoking history. There was a positive correlation between pathological grade and clinical stage (P < 0.05) and age (P < 0.05), and was positively correlated with age, smoking history and smoking history (P < 0.017) and Fuhrman grade (P < 0.045). 2. The methylation level of TCF21 gene in urine samples of renal cell carcinoma was significantly higher than that in normal urine samples, and the difference between them was statistically significant (P 0.05), and the methylation level of TCF21 in urine samples was different from that of different tumor sizes. There was a positive correlation between pathological grade and clinical stage (P < 0.05), and was positively correlated with the size of the tumor (P < 0.010) and the clinical stage (P < 0.017), and was positively correlated with the size of the tumor (P < 0.05) and the Fuhrman grade (P < 0.010) and the clinical stage (P < 0.05). 3.The area under the ROC curve of TCF21 methylation in renal cell carcinoma was higher than that in urine samples. The difference of TCF21 methylation level in renal cell carcinoma tissue and TCF21 methylation level in urine samples was statistically significant (P < 0.05). The diagnostic sensitivity and specificity of tissue sections were 89% and 89% respectively. The diagnostic sensitivity and specificity of urine samples were 79% and 100, respectively. Conclusion the level of TCF21 methylation in renal cell carcinoma may be used as an early diagnostic marker of renal cell carcinoma, and the level of TCF21 methylation may be associated with the development of renal cell carcinoma. There is an important relationship between malignancy and differentiation. Urine sample detection has the advantages of convenient collection, noninvasive and accurate detection. The noninvasive high-throughput methylation detection of urine samples can be used as an important supplement to tissue methylation detection. It can be used as an important method to determine the malignant degree and prognosis of renal cell carcinoma (RCC).
【學(xué)位授予單位】：福建醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R737.11

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本文編號：1617722