Let-7低表达与肺癌预后及HMGA2与肺癌发生发展相关性的meta分析

发布时间：2018-03-28 11:11

本文选题：肺癌　切入点：let-7　出处：《吉林大学》2016年硕士论文

【摘要】：研究背景及目的意义:肺癌是全世界范围内最常见的恶性肿瘤之一,发病率和死亡率均呈逐年上升趋势,近年来逐步发展为发病率最高的肿瘤,严重威胁着人类的生命健康。目前肺癌诊断的金标准是病理,病人明确诊断时多已处于晚期阶段。一些肿瘤标志物虽然可以帮助提高肺癌的早期诊断率及提示预后,但其特异性低,在临床应用时出现很多不确定性,从而导致患者直到处于晚期阶段才能明确诊断,大大的降低了患者的生存率。早期诊断及精确的预后分析是提高肺癌患者生存率的关键,所以能够找到一种可以及时反映肺癌的发生并准确预测患者预后情况的肿瘤标志物是至关重要的。Micro RNA的发现为预测肺癌的发生及预后开辟了新的思路。Micro RNA let-7的低表达与肺癌预后相关性已有多个报道,但研究结果不尽相同,与肺癌预后关系存在争议。在let-7抑癌机制中,研究最多的受let-7调控的基因是RAS及HMGA2。多项研究发现let-7能特异性抑制HMGA2表达,同时let-7作用HMGA2的靶向性优于RAS。在非小细胞肺癌组织中HMGA2的表达较正常肺组织增高,HMGA2在肺癌的发生发展过程中起着一定作用,HMGA2很可能成为肺癌诊断和治疗的新靶点。目前,国内外关于let-7的低表达与肺癌预后的关系,HMGA2在非小细胞癌肺癌发生发展中作用的文献已有多个研究报告,但各研究结果不尽一致,需要综合评价。本研究旨在应用meta分析方法整合数据,评价let-7的低表达与肺癌预后的相关性及HMGA2表达与肺癌关系的临床意义。研究方法:电子检索Pub Med、web of science、medline、cochrane library、Google scholar、CNKI、CBM、万方、维普等数据库,收集自建库以来已公开发表的分别关于let-7的低表达与肺癌预后及HMGA2与肺癌发生发展的相关性研究,语种限定为中文和英文,检索关键词为“肺癌、肺肿瘤、非小细胞肺癌、小细胞肺癌、肺腺癌、肺鳞癌、NSCLC、SCLC、lung cancer、let-7、micro RNA、预后(prognosis)”;“非小细胞肺癌、肺腺癌、肺鳞癌、NSCLC、lung adenocarcinoma、lung squamous cell carcinomas、HMGA2、HMGI-C、高迁移率族蛋白A2”。此外,也对相关文献所引用的参考文献进行了检索并筛查。判断是否符合文献纳入标准并进行质量评价,确定最终纳入的文献,随后提取各项研究中的相关数据,采用Stata SE12.0软件评价研究间的异质性,计算合并风险比值(hazard ratio,HR)及95%可信区间(confidence interval,CI)作为效应量来评价let-7的低表达与肺癌预后的相关性,HR1提示预后不良。计算合并比值比(odds ratio,OR)及95%CI作为效应量来评价HMGA2与肺癌发生发展的相关性。结果:1.最终纳入10篇关于let-7与肺癌预后的相关文献用于meta分析,均为NSCLC患者。总生存率作为临床结局。结果显示:let-7的低表达预示着较差的总生存率,风险比的合并值为1.55(95%CI:1.16-2.09,p0.05)。2.最终纳入9篇关于HMGA2与NSCLC发生发展的病例对照研究用于meta分析。结果显示:肺癌HMGA2的表达明显高于癌旁正常组织,HMGA2在肺癌组织的表达与肺癌TNM分期、有无淋巴结转移明显相关,而与其病理分类、性别、分化程度、肿瘤大小、吸烟与否之间的差异无统计学意义。结论:1.Let-7的低表达与肺癌的不良预后密切相关。本meta分析综合定量的分析了自各数据库建库以来所有相关文献。综上所述,Micro RNA let-7有望成为肺癌预后的新型肿瘤标志物。2.HMGA2表达的阳性率越高,肺癌发生的可能性就越大,就越具有侵袭性,因此HMGA2或许可能作为一种肺癌早期诊断的肿瘤标志物,为肺癌生物学行为以及预后的判断提供新思路,为肺癌的生物学治疗开辟新的途径。
[Abstract]:Research background and purpose: lung cancer is one of the most common malignant tumors worldwide, the morbidity and mortality are increasing year by year, in recent years, gradually developed into the highest incidence of cancer, a serious threat to human life and health. The current gold standard for the diagnosis of lung cancer is diagnosed pathology, patients have in the late stage. Although some tumor markers can help to improve the early diagnosis rate of lung cancer and the prognosis, but its specificity is low, there are many uncertainties in the clinical application, resulting in the late stage until the patients to confirm the diagnosis, greatly reduced the survival rate of patients. Early diagnosis and accurate prognosis analysis is the key to improve the survival rate of patients with lung cancer, so to find a can timely reflect the occurrence of lung cancer and predict the prognosis of patients with tumor markers are important to .Micro found RNA to predict the occurrence and prognosis of lung cancer and the prognosis of lung cancer has opened up the low expression of.Micro RNA let-7 correlation method for the multiple reports, but the results are not the same, there is a dispute with the prognosis of lung cancer. The mechanism of let-7 tumor suppressor, most of the research is the study of genes regulated by let-7 RAS a number of HMGA2. and found that let-7 can specifically inhibit the expression of HMGA2, expression of HMGA2 at the same time let-7 targeting HMGA2 is better than RAS. in non-small cell lung cancer tissues compared with normal lung tissue, HMGA2 in the occurrence and development of lung cancer plays a role, HMGA2 is likely to become a new target for diagnosis and treatment of lung cancer at present, the relationship between low expression and prognosis of lung cancer on let-7 at home and abroad, the occurrence and development of HMGA2 in non small cell lung cancer literature has a number of research reports, but the results are not consistent, need Comprehensive evaluation. This study aims to use the meta analysis method of data integration, the clinical significance of low expression of lung cancer and prognostic evaluation of let-7 and the correlation between the expression of HMGA2 and the risk of lung cancer. Methods: Med web of electronic searches of Pub, science, MEDLINE, Cochrane, library, Google, scholar, CNKI, CBM, Wanfang, VIP database. Study on the correlation between the collected since the establishment of the database published respectively on the low expression of let-7 and HMGA2 and the prognosis of lung cancer and lung cancer development, language is defined as Chinese and English, with key words of "lung cancer, lung cancer, non-small cell lung cancer, small cell lung cancer, lung adenocarcinoma, lung squamous cell carcinoma, NSCLC, SCLC. Lung cancer, let-7, micro RNA, (prognosis)"; "the prognosis of non-small cell lung cancer, lung adenocarcinoma, lung squamous cell carcinoma, NSCLC, lung adenocarcinoma, lung squamous cell carcinomas, HMGA2, HMGI-C, high mobility group protein A2. In addition, the Relevant literature references were searched and screened. Judge whether it meets the inclusion criteria and quality evaluation, to determine the final included literature, then all the relevant data in the study of extraction, using SE12.0 software to evaluate Stata heterogeneity between studies, computing with risk ratio (hazard ratio, HR) and 95% confidence the interval (confidence interval CI) to evaluate the relevance as effect of low expression of let-7 and prognosis of lung cancer, HR1 indicates poor prognosis. Calculate the pooled odds ratio (odds ratio OR) and 95%CI as the effect of the amount of correlation for the evaluation of HMGA2 and the occurrence and development of lung cancer. Results: 1. included 10 articles concerning let-7 and the prognosis of lung cancer for meta analysis, all NSCLC patients. The total survival rate as a clinical outcome. The result showed that the low expression of let-7 indicates that the poor overall survival rate, risk ratio with a value of 1.55 (95% CI:1.16-2.09, P0.05).2. 9 were included in the article on HMGA2 and the development of NSCLC case control study was used for meta analysis. The results showed that the expression of HMGA2 in lung cancer was significantly higher than that in normal tissues, the expression of HMGA2 in lung cancer and lung cancer TNM staging, lymph node metastasis significantly correlated with the pathological classification, gender. The degree of differentiation, tumor size, there was no significant difference between smoking. Conclusion: the low expression of 1.Let-7 and prognosis of lung cancer is closely related to the meta. The analysis of comprehensive quantitative analysis from the database since the relevant literature. In summary, the Micro RNA let-7 is expected to become a new tumor marker positive rate of lung cancer prognosis the expression of.2.HMGA2 is higher, the possibility of lung cancer is greater, more aggressive, so HMGA2 may be used as an early diagnosis of lung cancer tumor markers for lung cancer The evaluation of physical behavior and prognosis provides a new way of thinking, which opens new ways for the biological treatment of lung cancer.

【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R734.2

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