长链非编码RNA MEG3、GAS5在胃癌中的表达及其与预后的关系

发布时间：2018-02-04 16:14

本文关键词： 胃癌长链非编码RNA 母系表达基因3 生长特异抑制物5 实时荧光定量PCR　出处：《青岛大学》2017年硕士论文　论文类型：学位论文

【摘要】：目的:胃癌是危害人类健康的主要恶性肿瘤之一,也是全世界多发恶性肿瘤之一,其死亡率及复发率均较高。由于胃癌早期症状缺乏特异性,导致目前绝大多数胃癌在确诊时已属晚期,从而致使其病死率居高不下。目前胃癌的治疗手段主要是手术,新辅助化疗的应用使五年生存率有所上升,但总体效果仍不理想。随着分子生物学的发展,胃癌的早期诊断及分子靶向治疗成为研究的热点。近年来,一类称为长链非编码RNA(Long non-coding RNA,lnc RNA)的分子因在转录后调节、细胞生长、分化、增殖中承担重要作用而受到越来越多的关注。长链非编码RNA与肿瘤发生发展的关系成为研究的热点。本实验研究长链非编码RNA母系表达基因3(Maternally Expressed Gene 3,MEG3)、生长特异抑制物5(Growth arrest-specific 5,GAS5)在胃癌组织中的表达,分析两者与预后的关系,并进一步探讨MEG3同凋亡相关蛋白P53、MDM2之间的相关性,为胃癌的早期发现及指导预后提供理论依据。方法:收集青岛市市立医院普外科2012年9月--2013年6月行手术治疗的胃癌切除标本(包括癌组织及对应的远端正常组织)55例,采用实时荧光定量PCR法检测胃癌组织及对应正常组织中MEG3、GAS5的表达,并分析其与胃癌临床病理参数及预后的关系;蛋白免疫印迹法(Western blot)检测胃癌组织中P53和MDM2蛋白的表达水平,进一步分析两者与MEG3的相关性。结果:1.Lnc RNA MEG3在胃癌组织的相对表达水平(7.98±0.19)低于所对应的正常组织(9.47±0.18),(P0.05)。2.Lnc RNA GAS5在胃癌组织的相对表达水平(4.03±0.18)低于所对应的正常组织(6.06±0.18),(P0.05)。3.MEG3和GAS5的相对表达水平与是否淋巴结转移、分化程度及TNM分期相关。4.P53与MEG3的表达呈正相关(r=0.591,P0.05);MDM2与MEG3的表达呈负相关(r=-0.346,P0.05)。5.MEG3、GAS5高水平表达者较低水平表达者中位生存期明显延长。结论:1.MEG3、GAS5在胃癌发生发展过程中发挥抑癌基因的作用。2.MEG3与P53、MDM2在胃癌发生、发展的生物学机制上有重要联系。3.检测MEG3、GAS5的表达水平对评估胃癌预后有潜在价值。
[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 卤0.19, which was lower than that in normal tissues (P < 0.05). 9.47 卤0.18). The relative expression level of LNC RNA GAS5 in gastric cancer was 4.03 卤0.18), which was lower than that in normal tissues (6.06 卤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.
【学位授予单位】：青岛大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R735.2

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