Notch信號通路在直腸癌的表達及作用影響
發(fā)布時間:2018-03-01 15:05
本文關(guān)鍵詞: 直腸癌 Notch信號通路 Notch-1 Jagged-1 Hes-1 出處:《河北醫(yī)科大學(xué)》2017年碩士論文 論文類型:學(xué)位論文
【摘要】:目的:檢測Notch信號通路中Notch-1、Jagged-1及Hes-1因子在直腸癌組織及癌旁正常組織中的表達情況變化,探討三者之間相互作用關(guān)系及對直腸癌侵襲及轉(zhuǎn)移的影響。方法:本實驗采用Real-Time PCR方法檢測2016年8月至11月河北醫(yī)科大學(xué)第四醫(yī)院40名直腸癌患者手術(shù)標(biāo)本中直腸癌組織和癌旁正常組織的Notch-1表達水平的差異并分析不同臨床特征狀態(tài)下該因子的變化趨勢;同時采用Western Blot方法檢測同一樣本中直腸癌組織和癌旁正常組織中的Jagged-1和Hes-1的表達水平的變化。運用統(tǒng)計學(xué)軟件SPSS21.0對檢測結(jié)果進行分析。結(jié)果:1采用Real-Time PCR技術(shù)對Notch-1在直腸癌組織及癌旁正常組織中的表達水平進行檢測,結(jié)果發(fā)現(xiàn)Notch-1在直腸癌組織中的表達量為0.003054±0.0005337,在癌旁正常組織中的表達量為0.0006564±0.0001491,t值為4.327,P值為0.0049,兩組數(shù)據(jù)差異具有統(tǒng)計學(xué)意義(P0.05),說明直腸癌組織的Notch-1表達水平明顯高于癌旁正常組織。2根據(jù)患者性別、年齡、淋巴結(jié)轉(zhuǎn)移情況、TNM分期、分化程度五種臨床特征對樣本進行分層分析,分別計算各層樣本中Notch-1在直腸癌組織中的表達情況,結(jié)果如下:按性別分組:男性(0.003394±0.0003704),女性(0.003515±0.0003992),t=0.16,P=0.851;按年齡分組:64歲以上(0.003421±0.0003617),64歲以下(0.003510±0.0003747),t=0.97,P=0.305;按淋巴結(jié)轉(zhuǎn)移情況:有淋巴結(jié)轉(zhuǎn)移(0.003854±0.0003459),無淋巴結(jié)轉(zhuǎn)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在直腸癌中的表達情況與腫瘤的淋巴結(jié)轉(zhuǎn)移情況,TNM分期及分化程度有關(guān),而與性別和年齡無關(guān)。3用Western Blot技術(shù)分別檢測直腸癌組織及癌旁正常組織中Jagged-1蛋白的表達并對兩組數(shù)據(jù)進行比較,t=25.45,P=0.001(0.05),差異有統(tǒng)計學(xué)意義。結(jié)果顯示直腸癌組織中Jagged-1的表達明顯高于癌旁正常組織。4用Western Blot技術(shù)分別檢測直腸癌組織及癌旁正常組織中Hes-1的表達并對兩組數(shù)據(jù)進行比較,t=35.64,P=0.0089(0.05),差異有統(tǒng)計學(xué)意義,結(jié)果顯示直腸癌組織中Hes-1的表達明顯高于癌旁正常組織。5將Notch-1在直腸癌組織中的表達情況與Jagged-1在直腸癌組織中的表達情況進行相關(guān)性分析,得到r=0.64,當(dāng)校驗水準(zhǔn)α=0.05時,r=0.30,可知Notch-1的表達與Jagged-1在直腸癌組織的表達存在正相關(guān),將Notch-1在直腸癌組織中的表達情況與Hes-1在直腸癌組織中的表達情況進行相關(guān)性分析,得到r=0.45,當(dāng)校驗水準(zhǔn)α=0.05時,r=0.30,可知在直腸癌中,Notch-1的表達與Hes-1的表達也存在正相關(guān)聯(lián)系。結(jié)論:1在Notch信號通路中,Notch-1,Jagged-1和Hes-1在直腸癌組織中高表達,且明顯高于癌旁正常組織,可能與直腸癌的發(fā)生發(fā)展有關(guān),并有可能成為直腸癌潛在的治療靶點。2 Notch-1的表達與腫瘤的淋巴結(jié)轉(zhuǎn)移情況,TNM分期及分化程度有關(guān),提示其可能對直腸癌的侵襲和轉(zhuǎn)移有影響,檢測Notch-1定量對于直腸癌的早期診斷及預(yù)后具有一定的參考價值。3 Notch-1與Jagged-1、Hes-1在直腸癌組織中的表達存在正相關(guān)性關(guān)系,提示三者可能通過相互作用影響而共同對Notch信號通路進行調(diào)控,并有可能成為直腸癌治療的潛在靶點。
[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.
【學(xué)位授予單位】:河北醫(yī)科大學(xué)
【學(xué)位級別】:碩士
【學(xué)位授予年份】:2017
【分類號】:R735.37
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