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長鏈非編碼RNA MEG3、GAS5在胃癌中的表達及其與預后的關系

發(fā)布時間:2018-02-04 16:14

  本文關鍵詞: 胃癌 長鏈非編碼RNA 母系表達基因3 生長特異抑制物5 實時熒光定量PCR 出處:《青島大學》2017年碩士論文 論文類型:學位論文


【摘要】:目的:胃癌是危害人類健康的主要惡性腫瘤之一,也是全世界多發(fā)惡性腫瘤之一,其死亡率及復發(fā)率均較高。由于胃癌早期癥狀缺乏特異性,導致目前絕大多數(shù)胃癌在確診時已屬晚期,從而致使其病死率居高不下。目前胃癌的治療手段主要是手術,新輔助化療的應用使五年生存率有所上升,但總體效果仍不理想。隨著分子生物學的發(fā)展,胃癌的早期診斷及分子靶向治療成為研究的熱點。近年來,一類稱為長鏈非編碼RNA(Long non-coding RNA,lnc RNA)的分子因在轉錄后調(diào)節(jié)、細胞生長、分化、增殖中承擔重要作用而受到越來越多的關注。長鏈非編碼RNA與腫瘤發(fā)生發(fā)展的關系成為研究的熱點。本實驗研究長鏈非編碼RNA母系表達基因3(Maternally Expressed Gene 3,MEG3)、生長特異抑制物5(Growth arrest-specific 5,GAS5)在胃癌組織中的表達,分析兩者與預后的關系,并進一步探討MEG3同凋亡相關蛋白P53、MDM2之間的相關性,為胃癌的早期發(fā)現(xiàn)及指導預后提供理論依據(jù)。方法:收集青島市市立醫(yī)院普外科2012年9月--2013年6月行手術治療的胃癌切除標本(包括癌組織及對應的遠端正常組織)55例,采用實時熒光定量PCR法檢測胃癌組織及對應正常組織中MEG3、GAS5的表達,并分析其與胃癌臨床病理參數(shù)及預后的關系;蛋白免疫印跡法(Western blot)檢測胃癌組織中P53和MDM2蛋白的表達水平,進一步分析兩者與MEG3的相關性。結果:1.Lnc RNA MEG3在胃癌組織的相對表達水平(7.98±0.19)低于所對應的正常組織(9.47±0.18),(P0.05)。2.Lnc RNA GAS5在胃癌組織的相對表達水平(4.03±0.18)低于所對應的正常組織(6.06±0.18),(P0.05)。3.MEG3和GAS5的相對表達水平與是否淋巴結轉移、分化程度及TNM分期相關。4.P53與MEG3的表達呈正相關(r=0.591,P0.05);MDM2與MEG3的表達呈負相關(r=-0.346,P0.05)。5.MEG3、GAS5高水平表達者較低水平表達者中位生存期明顯延長。結論:1.MEG3、GAS5在胃癌發(fā)生發(fā)展過程中發(fā)揮抑癌基因的作用。2.MEG3與P53、MDM2在胃癌發(fā)生、發(fā)展的生物學機制上有重要聯(lián)系。3.檢測MEG3、GAS5的表達水平對評估胃癌預后有潛在價值。
[Abstract]:Objective: gastric cancer is one of the major malignant tumors endangering human health and one of the most common malignant tumors in the world. The mortality rate and recurrence rate of gastric cancer are high because of the lack of specificity of early symptoms of gastric cancer. At present, the majority of gastric cancer at the time of diagnosis has been advanced, resulting in a high mortality. At present, the main treatment for gastric cancer is surgery, the use of neoadjuvant chemotherapy has increased the five-year survival rate. With the development of molecular biology, the early diagnosis and molecular targeted therapy of gastric cancer have become a hot topic in recent years. A class of molecules known as long chain noncoding RNA(Long non-coding RNAs (LNNRNAs) are responsible for posttranscriptional regulation, cell growth and differentiation. The relationship between long chain noncoding RNA and tumorigenesis and development has become a hot topic. In this study, we studied the long chain non coding RNA maternal expression gene 3 (. Maternally Expressed Gene 3. The expression of MEG3, growth arrest-specific 5 (GAS5) in gastric carcinoma was analyzed. The relationship between the expression of MEG3 and prognosis was analyzed. The relationship between MEG3 and apoptosis-related protein P53 / MDM2 was further investigated. To provide theoretical basis for early detection and prognosis of gastric cancer. Methods: the surgical specimens of gastric cancer from September 2012 to June 2013 in general surgery department of Qingdao City Hospital were collected. There were 55 cases of cancer tissues and corresponding distal normal tissues. The expression of MEG3GAS5 in gastric cancer tissues and corresponding normal tissues was detected by real-time fluorescence quantitative PCR, and the relationship between MEG3GAS5 expression and clinicopathological parameters and prognosis of gastric cancer was analyzed. Western blot was used to detect the expression of p53 and MDM2 protein in gastric carcinoma. Results 1. The relative expression level of LNC RNA MEG3 in gastric cancer was 7.98 鹵0.19, which was lower than that in normal tissues (P < 0.05). 9.47 鹵0.18). The relative expression level of LNC RNA GAS5 in gastric cancer was 4.03 鹵0.18), which was lower than that in normal tissues (6.06 鹵0.18). The relative expression level of MEG3 and GAS5 and lymph node metastasis. The degree of differentiation and the correlation of TNM staging. 4. P53 were positively correlated with the expression of MEG3. There was a negative correlation between the expression of MDM2 and MEG3. The median survival time of the patients with high GAS5 expression was significantly longer than that with lower GAS5 expression. Conclusion: 1. GAS5 plays an important role in the carcinogenesis and development of gastric cancer. 2. MEG3 and P53 MDM2 play an important role in carcinogenesis and development of gastric cancer. 3. Detection of MEG3. The expression of GAS5 has potential value in evaluating the prognosis of gastric cancer.
【學位授予單位】:青島大學
【學位級別】:碩士
【學位授予年份】:2017
【分類號】:R735.2

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