Notch信号通路在直肠癌的表达及作用影响

发布时间：2018-03-01 15:05

本文关键词： 直肠癌 Notch信号通路 Notch-1 Jagged-1 Hes-1　出处：《河北医科大学》2017年硕士论文　论文类型：学位论文

【摘要】：目的:检测Notch信号通路中Notch-1、Jagged-1及Hes-1因子在直肠癌组织及癌旁正常组织中的表达情况变化,探讨三者之间相互作用关系及对直肠癌侵袭及转移的影响。方法:本实验采用Real-Time PCR方法检测2016年8月至11月河北医科大学第四医院40名直肠癌患者手术标本中直肠癌组织和癌旁正常组织的Notch-1表达水平的差异并分析不同临床特征状态下该因子的变化趋势;同时采用Western Blot方法检测同一样本中直肠癌组织和癌旁正常组织中的Jagged-1和Hes-1的表达水平的变化。运用统计学软件SPSS21.0对检测结果进行分析。结果:1采用Real-Time PCR技术对Notch-1在直肠癌组织及癌旁正常组织中的表达水平进行检测,结果发现Notch-1在直肠癌组织中的表达量为0.003054±0.0005337,在癌旁正常组织中的表达量为0.0006564±0.0001491,t值为4.327,P值为0.0049,两组数据差异具有统计学意义(P0.05),说明直肠癌组织的Notch-1表达水平明显高于癌旁正常组织。2根据患者性别、年龄、淋巴结转移情况、TNM分期、分化程度五种临床特征对样本进行分层分析,分别计算各层样本中Notch-1在直肠癌组织中的表达情况,结果如下:按性别分组:男性(0.003394±0.0003704),女性(0.003515±0.0003992),t=0.16,P=0.851;按年龄分组:64岁以上(0.003421±0.0003617),64岁以下(0.003510±0.0003747),t=0.97,P=0.305;按淋巴结转移情况:有淋巴结转移(0.003854±0.0003459),无淋巴结转移(0.002985±0.0003571),t=3.52,P=0.001;按TNM分期:T1-T2(0.002814±0.0004542),T3-T4(0.003954±0.0005172),t=3.35,P=0.002;按分化程度:高中分化(0.003031±0.0004012),低分化(0.004120±0.0004581),t=3.26,P=0.003。由此可知,Notch-1在直肠癌中的表达情况与肿瘤的淋巴结转移情况,TNM分期及分化程度有关,而与性别和年龄无关。3用Western Blot技术分别检测直肠癌组织及癌旁正常组织中Jagged-1蛋白的表达并对两组数据进行比较,t=25.45,P=0.001(0.05),差异有统计学意义。结果显示直肠癌组织中Jagged-1的表达明显高于癌旁正常组织。4用Western Blot技术分别检测直肠癌组织及癌旁正常组织中Hes-1的表达并对两组数据进行比较,t=35.64,P=0.0089(0.05),差异有统计学意义,结果显示直肠癌组织中Hes-1的表达明显高于癌旁正常组织。5将Notch-1在直肠癌组织中的表达情况与Jagged-1在直肠癌组织中的表达情况进行相关性分析,得到r=0.64,当校验水准α=0.05时,r=0.30,可知Notch-1的表达与Jagged-1在直肠癌组织的表达存在正相关,将Notch-1在直肠癌组织中的表达情况与Hes-1在直肠癌组织中的表达情况进行相关性分析,得到r=0.45,当校验水准α=0.05时,r=0.30,可知在直肠癌中,Notch-1的表达与Hes-1的表达也存在正相关联系。结论:1在Notch信号通路中,Notch-1,Jagged-1和Hes-1在直肠癌组织中高表达,且明显高于癌旁正常组织,可能与直肠癌的发生发展有关,并有可能成为直肠癌潜在的治疗靶点。2 Notch-1的表达与肿瘤的淋巴结转移情况,TNM分期及分化程度有关,提示其可能对直肠癌的侵袭和转移有影响,检测Notch-1定量对于直肠癌的早期诊断及预后具有一定的参考价值。3 Notch-1与Jagged-1、Hes-1在直肠癌组织中的表达存在正相关性关系,提示三者可能通过相互作用影响而共同对Notch信号通路进行调控,并有可能成为直肠癌治疗的潜在靶点。
[Abstract]:Objective: to detect the Notch-1 in the Notch signaling pathway, Jagged-1 changes and factor Hes-1 in colorectal cancer and normal tissues the expression of interaction, exploring the relationship between the three and the effect on invasion and metastasis of colorectal cancer. Methods: in this experiment, and analyze the differences in expression level measured from August 2016 to November the fourth hospital of Hebei Medical University, 40 patients of rectal cancer samples of colorectal cancer tissues and adjacent normal tissues using Notch-1 Real-Time PCR method. The changes of the factor state of different clinical characteristics; expression level changes at the same time using Western Blot method for detection of colorectal cancer tissue of the same sample and adjacent normal tissues of Jagged-1 and Hes-1. Using the statistical software SPSS21.0 for detection results results: 1 using Real-Time PCR technology of Notch-1 in colorectal cancer tissues and adjacent normal tissues The level of testing, results showed that the expression of Notch-1 in rectal cancer was 0.003054 + 0.0005337, the expression in cancer tissues was 0.0006564 + 0.0001491, t = 4.327, P = 0.0049, statistically significant differences between the two groups of data (P0.05), that the expression level of Notch-1 was significantly higher than that in colorectal cancer tissues cancerous tissue.2 according to gender, age, lymph node metastasis, TNM staging, differentiation degree of five kinds of clinical characteristics of the sample were stratified analysis, each layer of the Notch-1 sample in rectal cancer was calculated, the results are as follows: grouped by gender: male (0.003394 + 0.0003704), female (0.003515 + 0.0003992), t=0.16, P=0.851; according to the age: 64 years old (0.003421 + 0.0003617), under 64 years of age (0.003510 + 0.0003747), t=0.97, P=0.305; according to the transfer of lymph node, lymph node metastasis (0.003854 + 0.000345 9), without lymph node metastasis (0.002985 + 0.0003571), t=3.52, P=0.001; according to TNM staging: T1-T2 (0.002814 + 0.0004542), T3-T4 (0.003954 + 0.0005172), t=3.35, P=0.002; according to the degree of differentiation: high differentiation (0.003031 + 0.0004012), low differentiation (0.004120 + 0.0004581), t=3.26, P=0.003. so, the expression of Notch-1 in rectal cancer with lymph node metastasis, TNM staging and the degree of differentiation, and gender and age has nothing to do with Western.3 Blot technology was used to detect the expression of Jagged-1 protein in colorectal cancer and normal tissues and compare the data of two group were t=25.45, P=0.001 (0.05), a significant difference. The results showed that the expression of Jagged-1 in rectal cancer was significantly higher than that in normal tissues using.4 Western Blot technique was used to detect the expression of Hes-1 in colorectal cancer and normal tissues and to compare two sets of data, T=35.64, P=0.0089 (0.05), the difference was statistically significant, the results showed that the expression of Hes-1 in rectal cancer tissues was significantly higher than that of adjacent normal tissue.5 expression of Notch-1 in colorectal cancer tissues and the expression of Jagged-1 in colorectal cancer tissues by correlation analysis to r=0.64, when checking a =0.05 level, r=0.30, there are relative expression of Jagged-1 and Notch-1 in colorectal cancer tissues, the correlation analysis, expression of Notch-1 in colorectal cancer tissues and the expression of Hes-1 in colorectal cancer tissues by r=0.45, when checking a =0.05 level, r=0.30 in rectal cancer and expression of Hes-1 and Notch-1 have positive correlation conclusion: 1. In the Notch signaling pathway, Notch-1, Jagged-1 and Hes-1 are highly expressed in colorectal cancer tissues, and was significantly higher than in adjacent normal tissue, may be related to the occurrence of colorectal cancer Related to the development, and may become a potential therapeutic target for the treatment of rectal cancer the expression of.2 Notch-1 and lymph node metastasis, TNM staging and the degree of differentiation, suggesting that it may have effect on the invasion and metastasis of colorectal cancer, quantitative detection of Notch-1 Notch-1 and.3 have reference value for the early diagnosis of colorectal cancer Jagged-1 and fault prognosis and there is a positive correlation relationship between the expression of Hes-1 in colorectal cancer tissues, suggesting that the three may be affected by the interaction of common regulating Notch signaling pathway, and may become a potential target for the treatment of rectal cancer.

【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R735.37

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