本文關(guān)鍵詞： 腎細(xì)胞癌 SOX7 啟動子 甲基化 基因表達(dá)　出處：《河北醫(yī)科大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：目的:腎細(xì)胞癌(Renal Cell Carcinoma,RCC)是起源于腎實(shí)質(zhì)泌尿小管上皮系統(tǒng)的惡性腫瘤,簡稱腎癌,其發(fā)病率約為4/10萬,嚴(yán)重威脅著我國人群的健康。其發(fā)病原因尚不明確,可能與遺傳、肥胖、吸煙、高血壓以及抗高血壓治療有關(guān)。研究發(fā)現(xiàn)表觀遺傳學(xué)改變可以影響基因的表達(dá),而這可能與腫瘤的發(fā)生、發(fā)展有著密切的關(guān)系。目前,研究較深入的是表觀遺傳學(xué)中的基因甲基化與腫瘤間的關(guān)系。SOX7屬于SOXF亞族,參與調(diào)節(jié)多種發(fā)育過程,如脈管的形成、血液的形成、肌肉的發(fā)育等。近年來有研究結(jié)果表明在肺癌、乳腺癌、肝癌等惡性腫瘤中存在SOX7基因啟動子甲基化及SOX7m RNA表達(dá)異常,這可能是導(dǎo)致腫瘤發(fā)生以及發(fā)展的原因之一。然而目前尚無SOX7在RCC中相關(guān)報道。本研究通過特異性PCR及RT-PCR技術(shù)來分析SOX7基因異常甲基化與轉(zhuǎn)錄表達(dá)之間的關(guān)系,并通過統(tǒng)計學(xué)分析來研究SOX7基因異常甲基化與患者臨床數(shù)據(jù)之間的關(guān)系。初步探討SOX7基因異常甲基化在RCC中的作用。方法:1收集河北醫(yī)科大學(xué)第四醫(yī)院腎癌組織及正常組織標(biāo)本58例。采用反轉(zhuǎn)錄-聚合酶鏈反應(yīng)(Reverse Transcriptase-PCR,RT-PCR)來檢測58例RCC患者癌組織及正常組織中SOX7基因表達(dá)情況。2采用甲基化特異性PCR(Methylation Specific PCR,MSP)分析58例腎癌組織及正常腎組織中SOX7基因啟動子區(qū)的甲基化狀態(tài)。3使用統(tǒng)計學(xué)軟件SPSS20.0對實(shí)驗(yàn)數(shù)據(jù)進(jìn)行統(tǒng)計學(xué)分析。結(jié)果:1 SOX7在RCC組織和正常組織中存在完全甲基化、不完全甲基化、完全非甲基化三種不同的甲基化狀態(tài)。2 SOX7基因在RCC組織中甲基化陽性率為36.2%(21/58)高于正常組織標(biāo)本中的甲基化率陽性率10.3%(6/58),二者差異具有統(tǒng)計學(xué)意義(χ2=10.86 P=0.001);58例腎癌組織中,SOX7基因甲基化率在年齡(χ2=0.015 P=0.559)、性別(χ2=0.023P=0.547)、腫瘤大小(χ2=0.037 P=0.547)、Fuhrman核分級(χ2=0.514 P=0.773)四個方面沒有統(tǒng)計學(xué)差異(P值均大于0.05);在臨床分期(Ⅰ、Ⅱ期與Ⅲ、Ⅳ期)(P=0.035)方面存在統(tǒng)計學(xué)差異(P值小于0.05)。3腎癌組織中SOX7基因m RNA的相對表達(dá)量為0.35±0.06,低于正常組織標(biāo)本中的相對表達(dá)量0.62±0.07,經(jīng)過統(tǒng)計學(xué)分析,差異具有統(tǒng)計學(xué)意義(t=-22.679,P=0.001)。腎癌組織中,SOX7基因的相對表達(dá)量在年齡(t=1.359 P=0.182)、性別(t=-0.490 P=0.626)、腫瘤大小(t=-1.347 P=0.183)三方面沒有統(tǒng)計學(xué)差異(P值均大于0.05);在臨床分期(Ⅰ、Ⅱ期與Ⅲ、Ⅳ期)(t=-2.254,P=0.028)方面存在統(tǒng)計學(xué)差異(P值小于0.05)。4 58例患者在腎癌組織標(biāo)本方面,甲基化陽性患者SOX7基因m RNA的相對表達(dá)量為0.41±0.05,甲基化陰性患者SOX7基因m RNA的相對表達(dá)量為0.63±0.07,并且其差異存在統(tǒng)計學(xué)意義(t=-12.506,P=0.000)。結(jié)論:1腎癌組織中SOX7基因啟動子區(qū)高甲基化是頻發(fā)事件,并且腎癌組織中SOX7基因的甲基化率明顯高于正常腎組織,提示SOX7基因的異常甲基化可能是腎癌發(fā)生的主要機(jī)制之一。2腎癌組織中SOX7基因m RNA的相對表達(dá)量較正常組織低,提示SOX7基因在腎癌的發(fā)生發(fā)展可能起著抑癌基因的作用。3腎癌組織中甲基化陽性組SOX7m RNA的相對表達(dá)較非甲基化組低,提示SOX7基因甲基化有可能是導(dǎo)致其表達(dá)沉默的重要原因。
[Abstract]:Objective: renal cell carcinoma (Renal Cell, Carcinoma, RCC) is originated in the renal tubular epithelium of urinary system cancer, RCC, its incidence rate is about 4/10 million, a serious threat to our health. Its pathogenesis is not clear, may be related to heredity, obesity, smoking, hypertension and anti the treatment of hypertension. The study found that epigenetic changes can affect gene expression, which might be related to tumorigenesis is closely related to development. At present, in-depth study is the apparent relationship between.SOX7 gene methylation and tumor genetics in the SOXF subfamily belongs to, participate in the regulation of diverse developmental processes, such as vascular the formation of blood formation, muscle development. In recent years, the results of the study show that in lung cancer, breast cancer, SOX7 gene promoter methylation and SOX7m expression of RNA in abnormal liver cancer and other malignant tumors, which may lead to tumor One of the reasons for occurrence and development. However, there is no SOX7 in RCC reports. Through the study of specific PCR and RT-PCR technique to analyze the relationship between the expression of SOX7 gene methylation and transcription, and through statistical analysis to study the relationship between abnormal methylation of SOX7 gene in patients with clinical data. A preliminary study of SOX7 gene abnormality methylation in RCC. Methods: 1 collected from the fourth hospital of Hebei Medical University renal cell carcinoma and normal tissues of 58 cases. By using reverse transcription polymerase chain reaction (Reverse Transcriptase-PCR RT-PCR) to SOX7 were measured in 58 cases of RCC cancer tissue and normal tissue, the expression of.2 gene by methylation specific PCR (Methylation Specific PCR MSP, SOX7) analysis of 58 cases of renal cell carcinoma and normal renal tissue gene promoter methylation status of.3 using statistical software SPSS20.0 on experimental data Statistical analysis was performed. Results: 1 SOX7 methylation in RCC and normal tissue, incomplete methylation, completely unmethylated in three different methylation status of.2 gene methylation positive rate of SOX7 in RCC tissues was 36.2% (21/58) higher than the methylation positive rate of 10.3% normal tissues (6/58), two the difference was statistically significant (2=10.86 P=0.001); 58 cases of renal cell carcinoma, SOX7 gene methylation rate in age (2=0.015 P=0.559), gender (2=0.023P=0.547), tumor size (2=0.037 P=0.547), Fuhrman nuclear grade (2=0.514 P=0.773) had no statistically significant differences between the four aspects (the P values were greater than 0.05); the clinical stages (I, II and III, IV) (P=0.035) have significant differences (P value less than 0.05) the relative expression of SOX7 gene m.3 in renal cell carcinoma RNA was 0.35 + 0.06, lower than the relative expression of normal tissues 0.62 + 0.07, through statistical analysis, the difference was statistically significant (t=-22.679, P=0.001). Renal cell carcinoma, the expression of SOX7 (t=1.359 P=0.182) in the age, gender, tumor size (t=-0.490 P=0.626) (t=-1.347 P=0.183) three no statistical differences (P values were greater than 0.05) in the clinical stage; (I, II and III, IV) (t=-2.254, P=0.028) have significant differences (P value less than 0.05) of 58 cases of.4 patients in renal cell carcinoma tissues, the relative expression of methylation of SOX7 gene in patients with m the amount of RNA was 0.41 + 0.05, the relative expression of methylation of SOX7 gene in patients with m negative RNA the amount is 0.63 + 0.07, and the difference was statistically significant (t=-12.506, P=0.000). Conclusion: SOX7 1 renal cell carcinoma gene promoter hypermethylation is a frequent event, and the methylation rate of SOX7 gene in renal cell carcinoma was significantly higher than that in normal renal tissues, suggesting that SOX7 Aberrant methylation gene may be one of the main mechanisms of SOX7 relative expression of renal cell carcinoma of renal cell carcinoma.2 gene m RNA was lower than normal tissue, suggesting that SOX7 gene may play a role in.3 methylation of tumor suppressor gene in renal cell carcinoma of the positive group SOX7m RNA relative expression than unmethylated group on the occurrence and development of renal cell carcinoma that suggests that methylation of SOX7 gene may be an important reason lead to the expression of silence.

【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R737.11

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本文編號：1505258