Wnt信号通路关键抑制基因mRNA表达与胃癌的相关性研究

发布时间：2018-08-03 19:28

【摘要】：胃癌是一种严重威胁人们健康的多因素复杂疾病,在全世界的发病率仅次于肺癌、乳腺癌。虽然随着科技进步,胃癌的手术治疗已得到一定改善,但是由于该病的早期症状不明显,不易引起人们的注意,造成人们在就诊时已发展至晚期,使得该病的5年存活率只有20%-30%。为了提高胃癌的早期诊断与预防水平,寻找与胃癌发生相关的可靠分子标志物就显得尤为重要。而Wnt信号通路对于胃癌的发生起着非常重要的作用,该通路中一些抑制基因的的异常表达会使该通路活化,导致胃癌发生。因此本实验主要通过对Wnt信号通路中一些抑制基因(DKK1、DKK2、DKK3、 SFRP2、SFRP5、SFRP4、AXIN2、APC)表达的研究以及其表达水平与病理参数的相关性分析,力争探求胃癌诊断与预防的肿瘤分子标志物,从而为胃癌的提早判断及临床预测提供一定参考。实验中共收集40例符合要求的癌及癌旁组织,通过RT-PCR Taqman探针法检测Wnt抑制基因的表达,而后利用2-Act及2-△△ct公式对表达数据进行处理,最后将表达数据与临床病理数据进行统计分析。本课题主要得出以下结论：a、2-△c值经Mann-Whitney单尾非参数秩和检验后,发现DKK2(P0.0001)、SFRP2(P=0.049)、SFRP5(P=0.004)3个基因在胃癌发生中表达水平明显降低,；DKK1、DKK3、、SFRP4、、AXIN2、APC5个基因在两类组织中的相对表达没有明显差异,说明DKK2、SFRP2、SFRP5这3个基因的表达下调,对胃癌发生有着十分重要的作用;b、2-△△ct经非参数秩和检验结果显示,在胃癌中DKK、SFRP2、SFRP5这3个基因相比该通路中的其他基因表达明显下调,说明这3个基因可能在该通路活化中起着更为重要的作用;c、将表达结果与病理数据用t检验分析发现,这8个基因的差异表达都与年龄、性别和分化程度没有关系；但是DKKK1、DKK2、DKK3、SFRP2、SFRP4、APC这6个基因的表达水平与患者的临床分期显著相关；所有抑制剂的异常表达都同患者的lymph node转移在统计学上也具有显著性。综上所述,Wnt信号通路抑制基因的异常表达在胃癌的发生中起着重要作用,相关基因的表达下调与胃癌的发生及进展密切相关,其有可能作为胃癌早期诊断的分子标志物。
[Abstract]:Gastric cancer is a serious threat to human health, multifactorial and complex disease, the incidence of cancer in the world second only to lung cancer, breast cancer. Although the surgical treatment of gastric cancer has been improved with the progress of science and technology, the early symptoms of the disease are not obvious, and it is not easy to attract people's attention. As a result, people have developed to the late stage at the time of seeing a doctor, so that the 5-year survival rate of the disease is only 20-30%. In order to improve the level of early diagnosis and prevention of gastric cancer, it is very important to search for reliable molecular markers related to gastric cancer. The Wnt signaling pathway plays a very important role in the carcinogenesis of gastric cancer. The abnormal expression of some suppressor genes in this pathway may activate the pathway and lead to the occurrence of gastric cancer. In this study, we studied the expression of some inhibitory genes (DKK1, DK2, DKK3, SFRP5, SFRP4AXIN2APC) in the Wnt signaling pathway and analyzed the correlation between the expression level and pathological parameters in order to find out the tumor molecular markers for the diagnosis and prevention of gastric cancer. So as to provide a certain reference for early judgment and clinical prediction of gastric cancer. In the experiment, 40 cases of cancer and adjacent tissues were collected. The expression of Wnt suppressor gene was detected by RT-PCR Taqman probe method, and then the expression data were processed by 2-Act and 2ct formula. Finally, the expression data and clinicopathological data were statistically analyzed. The main conclusions of this study were as follows: after Mann-Whitney single tail nonparametric rank sum test, it was found that the relative expression of DKK2 (P0.0001) / SFRP2 (P0. 049) / SFRP5 (P0. 004) gene in gastric carcinogenesis was significantly lower than that of DKK1, DKK3SFRP4, AXIN2APC5 gene in two kinds of tissues. The results of nonparametric rank sum test showed that the expression of DKK2 / SFRP2 / SFRP5 gene was significantly down-regulated in gastric cancer compared with other genes in this pathway, and the results of nonparametric rank sum test showed that the expression of these three genes in gastric cancer was significantly down-regulated than that of other genes in this pathway, and the results of nonparametric rank sum test showed that the expression of these three genes in gastric cancer was significantly lower than that of other genes in this pathway. These three genes may play a more important role in the activation of the pathway. T test analysis showed that the differential expression of the eight genes had no relationship with age, sex and differentiation. However, the expression level of DKKK1, DKK2, DKK3, SFRP2 and SFRP4APC was significantly correlated with the clinical stage of the patients, and the abnormal expression of all inhibitors was statistically significant with the lymph node metastasis of the patients. In conclusion, the abnormal expression of Wnt signaling pathway suppressor gene plays an important role in the carcinogenesis of gastric cancer. The down-regulation of related genes is closely related to the occurrence and progression of gastric cancer, which may be used as a molecular marker for early diagnosis of gastric cancer.
【学位授予单位】：西北大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R735.2

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