孤儿核受体基因Nurr1在胃癌、结肠癌中的表达及意义

发布时间：2018-03-08 16:46

本文选题：孤儿核受体　切入点：Nurr1　出处：《复旦大学》2014年硕士论文　论文类型：学位论文

【摘要】：目的：胃癌、结肠癌均为临床上最常见的恶性肿瘤之一。在全球范围内,胃癌、结肠癌的发病率和死亡率均较高。近年来,随着人民生活水平的不断提高,饮食习惯和饮食结构的改变,特别是冰箱的广泛应用,胃癌的发病率有所下降,而结肠癌的发病率却在我国呈逐年上升趋势。胃癌、结肠癌还可以引起梗阻、穿孔等严重的并发症,即使经过常规放化疗、手术等治疗,但肿瘤病人,尤其是晚期病人的生存率仍不够理想。因此,加大对胃癌、结肠癌的基础研究,深入探讨其发生、发展及浸润转移的机理,显得尤为迫切重要。孤儿核受体家族为即早基因,属于类固醇类激素、甲状腺激素核受体超家族,主要表达在中枢神经系统内,可被环境中的刺激信号快速诱导,作为非配体依赖的转录因子和早期反应基因行使功能,与胚胎发育早期神经系统的发育和分化密切相关。近年来,对孤儿核受体家族及其成员的研究,是分子生物学、临床医学以及药理学等众多相关领域的研究热点。目前已经发现的孤儿核受体家族成员包括Nurr1、Nur77和NOR-1三种基因。他们除了共同参与调节基因表达及神经细胞的生存、发展、分化以外,在各自的分布器官／组织中亦发挥着重要作用。近几年的研究表明,孤儿核受体家族成员不仅在正常机体组织中有所表达,而且在肿瘤的发生、发展过程中有着重要作用。例如,Nur77在细胞核内有促进胃癌细胞生长的作用。当受到某种机制的调控时,其靶点会转移至线粒体,这会改变Nur77的促生长表型,最终触发细胞色素C的释放,导致细胞凋亡；NOR-1可使BP17基因表达上调,纤维细胞生长因子结合蛋白分泌增多而促进肝癌血管生成。而Nurr1在胃癌、结肠癌中的作用尚未有明确的定论。我们利用免疫组织化学方法,对孤儿核受体家族成员Nurr1在胃癌、结肠癌中的表达情况及其与肿瘤生物学行为和患者预后之间的关系、作用机制进行研究,为胃癌结肠癌治疗药物和转移复发机制的研究提供可能的靶点。材料与方法：对本院2008年进行根治性手术切除的胃癌、结肠癌病人进行随访,从中选取具有完整临床及随访资料的病例,其中胃癌病人78例,结肠癌病人76例。我们使用免疫组织化学(SABC)方法对所选病人的石蜡切片进行染色,然后对染色结果统计分析。具体而言,选取4例正常胃组织中的染色情况,以此作为基准进而观察Nurr1在胃癌及癌周正常组织中的表达强度。选取3例结肠正常组织中的染色情况,以此为对照观察结肠癌、癌周组织中Nurr1的表达情况。然后从肿瘤分化程度、TNM分期等方面对各组病例进行分类,统计Nurr1免疫组化结果与胃癌、结肠癌的分化程度、TNM分期等的关系,并进一步分析Nurr1的表达强度与患者生存率之间有无相关性。结果：Nurr1在正常胃粘膜细胞及癌周组织中表达较弱；在胃癌细胞中有且表达较强,其表达与肿瘤的分期呈正相关；Nurr1在伴有淋巴结或远处转移、TNM晚期的肿瘤中表达较强；Nurr1表达越强的胃癌患者预后越差。Nurr1在正常结肠细胞及癌周组织中表达较弱；在结肠癌细胞中有且表达较强,其表达与肿瘤的分期呈正相关；Nurr1在伴有淋巴结或远处转移、TNM晚期的肿瘤中表达较强；Nurr1表达越强的结肠癌患者预后越差。结论：Nurr1在胃癌、结肠癌中表达较高,其表达强度与肿瘤的淋巴结转移情况,分期等生物学行为之间存在显著正相关,Nurr1在胃癌、结肠癌中的表达与患者的预后有关,表达越高,其预后越差。
[Abstract]:Objective: gastric cancer, colon cancer is one of the most common malignant tumors. Clinical gastric cancer worldwide, colorectal cancer incidence and mortality are high. In recent years, with the improvement of people's life, eating habits and diet changes, especially the wide application of the refrigerator, the incidence of gastric cancer decreased, and the incidence of colon cancer in China has increased year by year. Gastric cancer, colon cancer can also cause obstruction, perforation and other serious complications, even after conventional chemotherapy, surgery and other treatment, but the survival rate of cancer patients, especially the patients in advanced stage is still not ideal. Therefore, increase on gastric cancer. Basic research of colorectal cancer, to explore its occurrence, development and mechanism of invasion and metastasis, is particularly important. For early gene orphan nuclear receptor family, which belongs to the steroid hormone, thyroid hormone nuclear receptor superfamily, Lord To express in the central nervous system, can be rapidly induced stimuli in the environment, as a ligand dependent transcription factor genes and early response function, and is closely related to early embryonic development and differentiation of the nervous system. In recent years, the research on the orphan nuclear receptor family and its members, molecular biology, research hotspot clinical medicine and pharmacology and many other related fields. It was found that the orphan nuclear receptor family members including Nurr1, Nur77 and NOR-1 three genes. In addition to their outside might participate in the regulation of gene expression and neuronal survival, development, differentiation, also plays an important role in the distribution of organ / tissue in their recent research. Years indicated that the orphan nuclear receptor family members not only in normal body tissues, and in tumor occurrence, development process plays an important role. For example, Nur7 7 in the nucleus has a function of promoting the growth of gastric cancer cells. When regulated by a mechanism, the target will be transferred to the mitochondria, which will change the growth phenotype of Nur77, eventually trigger the release of cytochrome C, leading to apoptosis; NOR-1 BP17 gene expression of fibroblast growth factor binding protein secretion increased angiogenesis and Nurr1 in gastric cancer, colon cancer has not been clarified. We use immunohistochemical method, the orphan nuclear receptor family member Nurr1 in gastric cancer, the relationship between the expression of colorectal carcinoma and its biological behavior and prognosis of tumors, study mechanism, provide a possible target for cancer therapeutics research and metastasis mechanism of node in gastric cancer. Materials and methods: in our hospital in 2008 for radical resection of gastric cancer and colon cancer patients. Were selected with complete clinical and follow-up data from cases, including 78 cases of patients with gastric cancer, 76 cases of colon cancer patients. We use immunohistochemistry (SABC) method of paraffin sections of selected patients were stained, and then statistical analysis. The staining results and specific staining, we selected 4 cases of normal stomach in the organization, as a benchmark and then observe the expression intensity of Nurr1 in gastric cancer and adjacent normal tissues were selected. 3 cases of normal colon tissues, as observed in colon cancer, the expression of Nurr1 in paracancerous tissues. Then the degree of tumor differentiation, TNM staging and classification of patients in each group Nurr1, the statistical results of immunohistochemistry and differentiation of gastric cancer, colon cancer, TNM staging, and further analysis there is no correlation between the expression intensity and the survival rate of Nurr1. Results: Nurr1 in normal The weak expression of gastric mucosal cells and cancerous peripheral tissue; and strong expression in gastric cancer cells, its expression stage was positively associated with tumor metastasis; Nurr1 in lymph node or distant, the strong expression of TNM in advanced tumor; the expression of Nurr1 in patients with gastric cancer prognosis is worse.Nurr1 weaker expression in normal colon cells and carcinoma; and strong expression in colon cancer cells, its expression stage was positively associated with tumor metastasis; Nurr1 in lymph node or distant, the strong expression of TNM advanced tumors; the more expression of Nurr1 in colon cancer patients with worse prognosis. Conclusion: high expression of Nurr1 in gastric cancer, colon cancer in its expression and lymph node metastasis, there was significant positive correlation between the stage of the biological behavior of Nurr1 in gastric cancer, colon cancer and expression in the prognosis of the patients, the higher the expression, its prognosis is Poor.

【学位授予单位】：复旦大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R735.2;R735.35

【共引文献】