本文選題：上皮性卵巢癌　切入點(diǎn)：Micro　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:Micro RNA(mi RNA)是近年來發(fā)現(xiàn)的一類高度保守的小分子非編碼RNA,長度約為22個(gè)核苷酸,人類基因組中有1/3以上基因是受其調(diào)控的。mi RNA通過與靶基因m RNA完全或不完全互補(bǔ)進(jìn)而抑制靶m RNA編碼的蛋白質(zhì)的合成。越來越多的研究結(jié)果表明,mi RNA在許多生物過程中具有重要作用,如胚胎發(fā)育、細(xì)胞分化與增殖、細(xì)胞凋亡、腫瘤的發(fā)展和激素分泌等。單核苷酸多態(tài)性(Single Nucleotide Polymorphism,SNP)是指在基因組水平上由于單個(gè)核苷酸的改變引起的DNA序列的多態(tài)性,在人類基因組中分布廣泛,是不同個(gè)體間最主要的遺傳變異。mi RNA在靶基因上的結(jié)合位點(diǎn)的SNP可以改變靶基因的表達(dá),從而影響患腫瘤的風(fēng)險(xiǎn)。SET8基因又稱為SETD8,PR-SET7或KMT5a,編碼組蛋白H4賴氨酸20單甲基轉(zhuǎn)移酶,這種酶通過甲基化組蛋白進(jìn)而調(diào)節(jié)基因的轉(zhuǎn)錄、細(xì)胞的生長周期及腫瘤的發(fā)生發(fā)展,SET8基因3'UTR的mi R-502結(jié)合區(qū)域內(nèi)存在rs16917496多態(tài)位點(diǎn),以往研究發(fā)現(xiàn)該位點(diǎn)多種腫瘤的發(fā)生和/或預(yù)后相關(guān)。本研究擬對(duì)SET8基因3’端非翻譯區(qū)單核苷酸多態(tài)性rs16917496與上皮性卵巢癌患者的發(fā)病風(fēng)險(xiǎn)、臨床特征及預(yù)后的相關(guān)性進(jìn)行研究,為上皮性卵巢癌的早期診斷尋找新的分子靶點(diǎn),并改善卵巢癌患者的預(yù)后。方法:1研究對(duì)象及隨訪選取100例2008年1月-2012年12月期間在河北醫(yī)科大學(xué)第二醫(yī)院進(jìn)行婦科手術(shù)且術(shù)后組織學(xué)病理證實(shí)為上皮性卵巢癌的石蠟切片包埋組織切片,100例患者術(shù)前未接受任何治療,詳細(xì)記錄患者相關(guān)臨床資料(包括年齡、臨床分期、殘留癌灶大小等),通過電話隨訪患者術(shù)后的生存情況,隨訪截止時(shí)間2014年12月31號(hào)。另選取在河北醫(yī)科大學(xué)第二醫(yī)院體檢健康的100例女性(除外與卵巢癌相關(guān)的疾病),獲得知情同意后,詳細(xì)記錄體檢資料,采集靜脈血備用。2基因組DNA提取、擴(kuò)增及測序:提取基因組DNA,DNA鑒定合格后,采用PCR技術(shù)擴(kuò)增目的片段,大小為299bp,上游引物為:5’-CCTGGTCAG TGGTCAGCAAAT-3’,下游引物為:5’-CTGGGAAAC ACGCTCAAAA TC-3’。產(chǎn)物經(jīng)瓊脂糖凝膠電泳證實(shí)后進(jìn)行雙向重復(fù)測序。3統(tǒng)計(jì)學(xué)分析:采用SPSS21.0統(tǒng)計(jì)軟件進(jìn)行統(tǒng)計(jì)學(xué)分析,采用χ2檢驗(yàn)或Fisher確切概率法比較計(jì)數(shù)資料。單因素分析使用Kaplan-Meier方法和Log-Rank方法,單因素分析中P值小于0.05的因素納入COX風(fēng)險(xiǎn)回歸模型進(jìn)行多因素分析。P0.05被認(rèn)為有統(tǒng)計(jì)學(xué)意義。結(jié)果:1在病例組與對(duì)照組之間,以基因型C/C為對(duì)照,與T/T基因型進(jìn)行比較,差異無統(tǒng)計(jì)學(xué)意義(P0.05),與C/T、C/T+T/T基因型進(jìn)行比較,差異有統(tǒng)計(jì)學(xué)意義(P㩳0.05),說明此位點(diǎn)與卵巢癌的發(fā)病風(fēng)險(xiǎn)相關(guān),C/C基因型卵巢癌的發(fā)病風(fēng)險(xiǎn)較低。2病例組中rs16917496位點(diǎn)各基因型與各臨床特征均無相關(guān)性,差異無統(tǒng)計(jì)學(xué)意義(P0.05)。3對(duì)上皮性卵巢癌患者進(jìn)行生存分析,SET8基因的rs16917496多態(tài)位點(diǎn)C/C、C/T、T/T基因型患者的3年生存率分別為80%、74.1%、58.5%,尚不能認(rèn)為此位點(diǎn)與上皮性卵巢癌患者的預(yù)后相關(guān)。4將單因素分析中有顯著性差異的納入COX模型進(jìn)行多因素分析,結(jié)果顯示,FIGO手術(shù)病理分期、殘留癌大小與上皮性卵巢癌患者的死亡風(fēng)險(xiǎn)相關(guān)。結(jié)論:1 SET8基因3’端非翻譯區(qū)的mi R-502結(jié)合位點(diǎn)單核苷酸多態(tài)性與上皮性卵巢癌的發(fā)病風(fēng)險(xiǎn)相關(guān)。2尚不能認(rèn)為SET8基因3'端非翻譯區(qū)mi R-502結(jié)合位點(diǎn)單核苷酸多態(tài)性與上皮性卵巢癌患者的預(yù)后相關(guān)。SET8基因的rs16917496位點(diǎn)基因型與上皮性卵巢癌患者的臨床特征)均沒有相關(guān)性。
[Abstract]:Objective: Micro RNA (MI RNA) is a recently discovered a highly conserved small molecule non encoding RNA, a length of about 22 nucleotides in the human genome contains more than 1/3.Mi RNA gene is under the control of the target gene m RNA complete or incomplete complementary protein synthesis and inhibition of target m RNA encoding. More and more studies show that MI RNA plays an important role in many biological processes, such as embryonic development, cell differentiation and proliferation, apoptosis, tumor development and hormone secretion. Single nucleotide polymorphisms (Single, Nucleotide Polymorphism, SNP) is a polymorphic DNA sequence caused by a single nucleotide change in the on genome level, widely distributed in the human genome,.Mi RNA is the main genetic variation among different individuals in the SNP binding sites of target gene can alter the expression of target genes, thus affecting the patient The risk of.SET8 gene is also known as SETD8, PR-SET7 or KMT5a, encoding histone H4 lysine 20 methylation transferase, the enzyme by methylation of histone regulates gene transcription, cell cycle and the occurrence and development of tumor cells, SET8 gene 3'UTR mi R-502 polymorphism in rs16917496 binding region of memory. Previous research found that the sites of tumor and / or prognosis. This research focuses on the risk of SET8 gene 3 'end untranslated region single nucleotide polymorphism and rs16917496 in patients with epithelial ovarian cancer, the correlation of clinical features and prognosis were studied to find new molecular targets for early diagnosis of epithelial ovarian cancer, and improve the prognosis of patients with ovarian cancer. Methods: 1 subjects and follow-up from 100 cases of January 2008 December -2012 during gynecological surgery and postoperative histology in the second hospital of Hebei Medical University Pathology of epithelial ovarian cancer paraffin embedded tissue sections, 100 patients did not receive any treatment, with clinical data of the patients were recorded (including age, clinical stage, residual tumor size), survival through telephone follow-up after surgery, follow-up deadline in December 31, 2014. Another selection in 100 women in the second hospital of Hebei Medical University medical health (except those associated with ovarian cancer disease), after obtaining informed consent, a detailed record of the physical examination data, extraction of venous blood sampling alternate.2 genomic DNA, amplification and sequencing of genomic DNA extraction, DNA: identification of qualified after amplification by PCR, size 299bp, upstream primer for the 5 '-CCTGGTCAG TGGTCAGCAAAT-3', as the downstream primer: 5 '-CTGGGAAAC ACGCTCAAAA TC-3'. The product was confirmed by agarose gel electrophoresis after double to repeat sequence of.3 statistics Analysis: using the statistical analysis software SPSS21.0, comparison of count data using 2 test or Fisher's exact probability method. Single factor analysis using Kaplan-Meier method and Log-Rank method, single factor analysis of P value is less than 0.05 of the factors in COX regression model for multivariate analysis.P0.05 was considered statistically significant. Results: 1 in between the case group and the control group, the genotype C/C were compared with T/T genotype, the difference was not statistically significant (P0.05), and C/T, compared with C/T+T/T genotype, the difference was statistically significant (P? 0.05), the risk of this locus and ovarian cancer, the risk of C/C genotype of ovary the low rs16917496 of.2 cancer patients locus genotypes and the clinical features were not correlated, no statistically significant difference (P0.05).3 in patients with epithelial ovarian cancer were survival analysis, SET8 gene rs16917 496 polymorphic loci C/C, C/T, the 3 year survival rate of patients with T/T genotype were 80%, 74.1%, 58.5%, still can not believe that the multi factor analysis, were incorporated into the COX model.4 this site and prognosis in patients with epithelial ovarian cancer. The single factor analysis showed that there was significant difference, FIGO staging the residual risk of death, and the size of the cancer patients with epithelial ovarian cancer. Conclusion: 1 SET8 gene 3 'untranslated region of the MI R-502 with the risk associated with single nucleotide polymorphisms of.2 and epithelial ovarian cancer is the SET8 gene 3' untranslated region of MI R-502 combined with clinical features, prognosis of.SET8 gene and single nucleotide polymorphism in patients with epithelial ovarian cancer. The rs16917496 genotype in patients with epithelial ovarian cancer) are not related.

【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R737.31

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本文編號(hào)：1624077