CREPT与细胞周期D蛋白在非小细胞肺癌中的表达相关性及临床意义

发布时间：2018-01-24 14:40

本文关键词： 非小细胞肺癌 CREPT Cyclin D CDK4　出处：《第四军医大学》2015年硕士论文　论文类型：学位论文

【摘要】：目的:研究CREPT与细胞周期D蛋白在非小细胞肺癌组织及正常组织中的表达,分析CREPT和细胞周期D蛋白在非小细胞肺癌中表达的差异性及相关性,探讨CREPT和细胞周期D蛋白在NSCLC中的可能作用及其临床意义。方法:收集NSCLC组织271例,采用免疫组化法、Western Blot及PCR法检测NSCLC组织及相应正常组织中CREPT及细胞周期D相关蛋白的表达。结果:1.CREPT在271例NSCLC组织中表达阳性率为96.1%,而正常组织阳性率为30.4%,二者差异显著(P=0.000);CREPT表达与患者年龄、性别、吸烟与否、肿瘤大小及类型无显著差异性(P=0.380,0.627,0.894,0.253,0.638)。CREPT在NSCLC不同分化程度组间(P=0.000)、不同临床分期组间的表达差异性显著(P=0.025);在NSCLC总样本、腺癌样本中淋巴转移与否组间的表达差异性显著(P=0.003),而在鳞癌中的表达差异性不显著(P=0.166)。Kaplan-Meier生存分析和log-rank检验表明CREPT的表达与患者的生存期密切相关(P0.01)。多因素分析提示CREPT可能是判定非小细胞肺癌预后的独立生物学标志,HR为1.367(95%CI:1.085,1.723,p0.01)。Western Blot及PCR实验进一步证实了CREPT在NSCLC及其正常组织中的表达差异。2.Cyclin D1、Cyclin D2、Cyclin D3、CDK4在NSCLC组织和正常组织中的表达差异性显著(P=0.000);Cyclin D3、CDK4的表达在NSCLC样本的不同分化程度、不同TNM分期、淋巴转移与否组间的表达差异性显著(P0.01);而Cyclin D2在腺癌的不同分化程度间表达差异性显著(P0.05);Cyclin D1仅在腺癌的不同临床分期间的表达差异性显著(P0.01)。3.在NSCLC肿瘤组织中CREPT表达与Cyclin D1、Cyclin D2、Cyclin D3、CDK4、Ki67表达的相关系数分别为0.295、0.338、0.458、0.520、0.621,P值均为0.000,即CREPT的表达与Cyclin D1、Cyclin D2的表达相关性不显著,而CREPT与Cyclin D3、CDK4、Ki67的表达相关性显著;NSCLC的低分化组或III-IV期患者中,CREPT表达与Cyclin D3、CDK4、Ki67的表达相关性显著(P0.01)。结论:1.CREPT、细胞周期D相关蛋白在NSCLC中过表达,均为NSCLC组织和正常组织中的差异性蛋白。2.CREPT的表达在NSCLC的不同分级、分期及淋巴转移与否组间的差异性显著,表明CREPT在NSCLC发生发展的进程中起重要作用。结合生存分析显示CREPT的表达与患者的生存期密切相关提示CREPT可作为独立判断NSCLC预后的生物学标志。3.Cyclin D3、CDK4在NSCLC的不同分级间、分期间及淋巴转移与否组间的表达有显著性差异。4.本文结果显示在NSCLC中CREPT与Cyclin D1、Cyclin D2的相互作用较弱,而在低分化的NSCLC晚期患者的肿瘤组织中,CREPT与Cyclin D3、CDK4、Ki67的表达相关性显著,提示CREPT具有较强的促进细胞增殖的能力,可能通过上调Cyclin D3、CDK4的表达,协同加快细胞周期进程从而促进NSCLC的恶性进展。
[Abstract]:Objective: to study the expression of CREPT and cell cycle D protein in non-small cell lung cancer (NSCLC) and normal tissues. To analyze the difference and correlation between the expression of CREPT and cell cycle D protein in non-small cell lung cancer (NSCLC). To investigate the possible role of CREPT and cell cycle D protein in NSCLC and its clinical significance. Methods: 271 cases of NSCLC tissues were collected and immunohistochemical method was used. Western Blot and PCR were used to detect the expression of CREPT and cell cycle D related protein in NSCLC and normal tissues. 1. The positive rate of CREPT expression in 271cases of NSCLC was 96.1%. The positive rate of normal tissue was 30.4, and the difference between them was significant. There was no significant difference between CREPT expression and age, sex, smoking, tumor size and type. The expression of 0.638C 路crept in NSCLC with different differentiation degree was 0.0000.000, and the difference between different clinical stages was significant (P < 0.025). In the total NSCLC sample, there was significant difference in the expression of lymph node metastasis between the two groups (P0. 003). However, the difference of expression in squamous cell carcinoma was not significant (P = 0.166). Kaplan-Meier survival analysis and log-rank test showed that the expression of CREPT was closely related to survival time (P0.01). Multivariate analysis suggested that CREPT might be an independent biological marker for the prognosis of NSCLC. HR is 1.367 / 95CI: 1.085 / 1.723. The expression of CREPT in NSCLC and its normal tissues was further confirmed by p0.01 Blot and PCR assay. 2. Cyclin D1. The expression of Cyclin D2Cyclin D3 + CDK4 in NSCLC and normal tissues was significantly different. The expression of CDK4 in Cyclin D3 was significantly different in different differentiation degrees of NSCLC samples, different TNM stages, and the difference of the expression of CDK4 in lymphatic metastasis group was significant (P 0.01). The difference of Cyclin D2 expression in different differentiation degree of adenocarcinoma was significant (P 0.05). The difference of expression of Cyclin D1 was significant only in the different clinical stages of adenocarcinoma. The expression of CREPT and Cyclin D1 in the tumor tissue of NSCLC was significantly higher than that in the tumor tissue of NSCLC. The correlation coefficient of Cyclin D2Cyclin D3C3CDK4OK4 Ki67 expression was 0.2950.3380.458A0.520200.621, respectively. P values were 0.000, that is, the expression of CREPT was not correlated with the expression of Cyclin D1Cyclin D2, but CREPT and Cyclin D3. There was a significant correlation between the expression of CDK4 and Ki67. The expression of CREPT and Cyclin D3pCDK4 in low differentiation group or III-IV stage of NSCLC. The expression of Ki67 was significantly correlated with that of P0.01.Conclusion: 1. Creatine, D-associated protein of cell cycle is overexpressed in NSCLC. The expression of CREPT in NSCLC and normal tissues was significantly different in different grades, stages and lymphatic metastasis of NSCLC. It is suggested that CREPT plays an important role in the development of NSCLC. Combined with survival analysis, the expression of CREPT is closely related to the survival time of the patients. It is suggested that CREPT can be used as an independent judge of NS. Biological markers for the prognosis of CLC. 3. Cyclin. D3. There were significant differences in the expression of CDK4 between NSCLC grades, stages and lymphatic metastasis groups. 4. The results of this study showed that CREPT and Cyclin D1 were expressed in NSCLC. The interaction between Cyclin D2 and Cyclin D3 CDK4 was weak, while in the tumor tissues of poorly differentiated patients with NSCLC, CREPT and Cyclin D3 CDK4 were found. The expression of Ki67 was significantly correlated, suggesting that CREPT had a strong ability to promote cell proliferation, possibly by upregulating the expression of Cyclin D3pCDK4. To accelerate the progress of cell cycle and promote the malignant progress of NSCLC.
【学位授予单位】：第四军医大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R734.2

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