NOTUM基因在胃肠道肿瘤中的表达及临床意义

发布时间：2018-06-01 07:44

本文选题：胃癌 + 结肠癌　；参考：《中国人民解放军医学院》2017年硕士论文

【摘要】：背景胃肠道肿瘤严重危害着人类的健康,最新的ca杂志表明,在中国,胃癌在所有肿瘤中发病率和死亡率都高居第二位。虽然随着放疗化疗及免疫治疗的不断发展,胃癌的生存期有所延长。但是由于发现不及时,肿瘤大部分都在中晚期,使得胃癌的总体生存率不足30%。故早期发现胃癌及发现有效肿瘤标记物从而早期诊断早期防治是提高生存率的有效途径。NOTUM基因是一种新兴发现的基因,在斑马鱼中已经得到证实可以通过去磷酸化有效抑制wnt信号通路,而在人类肝癌中发现高表达,与wnt信号通路存在负反馈调节的作用。而在胃肠道肿瘤的研究尚未清晰,本研究探索NOTUM基因在结肠癌及胃癌中的表达及临床意义。目的检测NOTUM基因在胃癌组织中的表达情况,探讨其与胃癌患者的临床病理关系。研究wnt信号通路与NOTUM基因的相互影响关系,检测NOTUM基因在结肠癌组织中的表达情况,探讨其与结肠癌患者的临床病理关系。进一步探索NOTUM基因在消化道肿瘤中作用。方法收集胃癌及结肠癌组织标本,分别通过免疫组化方法检测组织中的NOTUM基因表达情况,分析NOTUM基因的表达与患者的临床病理及预后的关系,使用免疫印迹方法检测NOTUM蛋白与β-catenin蛋白的表达量,使用SPSS进行相关性分析确定NOTUM蛋白与β-catenin蛋白之间的关系。应用Kaplan-Meier方法比较NOTUM阳性表达胃癌患者与阴性表达胃癌患者在术后生存时间的差异。分别采用Log-rank检验和Cox回归模型对可能影响预后的临床病理特征进行单因素和多因素分析。结果(1)胃癌组织中NOTUM基因的表达显著增加,其表达与淋巴结转移及TNM分期及预后生存相关(p0.05),与患者的年龄、性别、肿瘤发生部位、肿瘤大小及肿瘤病理类型无关。胃癌组织中NOTUM基因和β-catenin蛋白的表达呈正相关。在NOTUM基因表达阳性的胃癌患者的生存时间明显缩短。NOTUM基因表达可以作为影响胃癌患者生存的独立危险因素(2)结肠癌组织中NOTUM基因的表达显著增加,其表达与淋巴结转移及TNM分期及预后生存相关(p0.05),与患者的年龄、性别、肿瘤大小及肿瘤病理类型无关。在NOTUM基因表达阳性的结肠癌患者的生存时间明显缩短。NOTUM基因表达可以作为影响结肠癌患者生存的独立危险因素结论胃癌及结肠癌中NOTUM基因在呈高表达,可作为判断胃癌及结肠癌患者疾病进展及预后的生物学标记物。
[Abstract]:Background Gastrointestinal cancer is a serious hazard to human health. The latest CA journal shows that gastric cancer is the second leading cause of morbidity and mortality among all tumors in China. Although with the continuous development of radiotherapy, chemotherapy and immunotherapy, gastric cancer survival has been prolonged. However, due to the late detection, most of the tumors are in the late stage, resulting in the overall survival rate of gastric cancer is less than 30. Therefore, the early detection of gastric cancer and the discovery of effective tumor markers for early diagnosis and prevention are effective ways to improve survival rate. NOTUM gene is a newly discovered gene. It has been proved that the wnt signaling pathway can be effectively inhibited by dephosphorylation in zebrafish, while high expression has been found in human hepatocellular carcinoma, and there is a negative feedback regulation with wnt signal pathway. The expression and clinical significance of NOTUM gene in colon cancer and gastric cancer were not clear. Objective to investigate the expression of NOTUM gene in gastric cancer and its clinicopathological relationship. To study the relationship between wnt signaling pathway and NOTUM gene, to detect the expression of NOTUM gene in colon cancer tissues, and to explore the clinicopathological relationship between NOTUM and colon cancer patients. To further explore the role of NOTUM gene in digestive tract tumors. Methods the expression of NOTUM gene was detected by immunohistochemical method in gastric and colon cancer tissues, and the relationship between the expression of NOTUM gene and clinicopathology and prognosis was analyzed. The expression of NOTUM protein and 尾 -catenin protein was detected by Western blot, and the relationship between NOTUM protein and 尾 -catenin protein was determined by SPSS correlation analysis. Kaplan-Meier method was used to compare the survival time of NOTUM positive expression gastric cancer patients and negative expression gastric cancer patients. Log-rank test and Cox regression model were used to analyze the clinicopathological features which may affect the prognosis. Results 1) the expression of NOTUM gene was significantly increased in gastric cancer tissues. The expression of NOTUM gene was correlated with lymph node metastasis, TNM stage and prognosis (P 0.05), but not with age, sex, tumor location, tumor size and tumor pathological type. There was a positive correlation between the expression of NOTUM gene and 尾-catenin protein in gastric carcinoma. The survival time of gastric cancer patients with positive NOTUM gene expression was significantly shortened. NOTUM gene expression could be used as an independent risk factor for the survival of gastric cancer patients. Its expression was correlated with lymph node metastasis, TNM stage and prognosis, but not with age, sex, tumor size and tumor pathological type. The survival time of colon cancer patients with positive NOTUM gene expression was significantly shortened. NOTUM gene expression may be an independent risk factor for the survival of colon cancer patients. Conclusion the expression of NOTUM gene is high in gastric cancer and colon cancer. It can be used as a biological marker to judge the progression and prognosis of gastric and colon cancer patients.
【学位授予单位】：中国人民解放军医学院
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R735

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