DEPDC1与甲状腺乳头状癌及BRAF基因突变的相关性研究

发布时间：2018-03-02 16:24

本文选题：DEPDC1　切入点：甲状腺乳头状癌　出处：《青岛大学》2017年硕士论文　论文类型：学位论文

【摘要】：背景:国内外大量研究表明目前甲状腺癌的发病率不断上升,而在甲状腺癌所有病理类型中乳头状甲状腺癌占半数以上。虽然甲状腺乳头状癌的致病因素目前仍不十分明确,但是几乎所有的恶性肿瘤均有正常细胞周期调节的缺失。分析调控细胞周期的DEPDC1蛋白与甲状腺乳头状癌及甲状腺乳头状癌中最重要的分子标记物BRAF基因的关联对甲状腺乳头状癌的发病机制研究具有重要意义。目的:研究甲状腺乳头状癌组织及瘤旁正常甲状腺组织中DEPDC1的表达情况,研究BRAF基因野生型甲状腺乳头状癌肿瘤组织中及BRAF基因突变型甲状腺乳头状癌肿瘤组织中DEPDC1表达差异情况,分析DEPDC1与甲状腺乳头状癌及BRAF基因突变及各临床特征之间的关系。为研究DEPDC1是否可以作为甲状腺乳头状癌的临床诊断及治疗靶点提供实验依据。方法:采用以医院临床标本为基础的对照研究,拟应用分子流行病学的方法,利用已有的标本提取组织蛋白及制作病理切片。应用免疫组化方法检测甲状腺乳头状癌肿瘤组织及瘤旁正常甲状腺组织中DEPDC1表达部位。应用免疫印迹法检测甲状腺乳头状癌肿瘤组织及瘤旁正常甲状腺组织、BRAF基因野生型肿瘤组织及BRAF基因突变型肿瘤组织中、不同临床特征分组甲状腺乳头状癌肿瘤组织中DEPDC1表达差异。结果:免疫组化结果显示DEPDC1在甲状腺乳头状癌及瘤旁正常组织中表达。在5例肿瘤组织病理切片中共检测到阴性表达1例,强阳性表达4例,2例瘤旁正常组织中均检测到弱阳性表达。DEPDC1蛋白定位于细胞核及细胞质中。免疫印迹结果显示DEPDC1蛋白在甲状腺乳头状癌肿瘤组织中表达情况为(59(14)62),免疫印迹结果显示DEPDC1蛋白在瘤旁组织表达情况为(14(14)20)。免疫印迹结果显示DEPDC1蛋白在甲状腺乳头状癌组织中表达量为(1.60±0.82),明显高于DEPDC1蛋白在瘤旁正常甲状腺组织中表达量(0.58±0.19)其差异有统计学意义(P0.05)。DEPDC1蛋白在BRAF基因突变型肿瘤组织中表达量为(1.83±0.80),明显高于在BRAF基因野生型肿瘤组织表达量(1.03±0.45)差异有统计学意义(P0.05)。男性患者及女性患者肿瘤组织中DEPDC1蛋白表达量分别为(1.41±0.71)、(1.64±0.83)该差异无统计学意义(P0.05)。年龄大于等于45岁及小于45岁患者肿瘤组织中DEPDC1蛋白表达量分别为(1.51±0.67)、(1.64±0.91)该差异无统计学意义(P0.05)。上述实验结果显示DEPDC1蛋白在甲状腺乳头状癌组织及瘤旁正常组织中均可检测到存在,且肿瘤组织中表达强度明显高于瘤旁正常甲状腺组织中表达强度,DEPDC1蛋白表达程度与甲状腺乳头状癌的特异性分子标记物突变型BRAF基因呈正相关,而DEPDC1蛋白的表达与性别、年龄等临床特征无明显关联。结论:DEPDC1蛋白定位于甲状腺乳头状癌细胞的细胞核及细胞质中,DEPDC1的表达与甲状腺乳头状癌及BRAF基因突变呈正相关,与性别及年龄无相关。
[Abstract]:Background: a large number of domestic and foreign research shows that the incidence of thyroid cancer is rising, while the nipple in thyroid cancer all pathological types of thyroid cancer accounts for more than half. Although the causative factors of papillary thyroid carcinoma is not very clear, but the lack of almost all malignant tumors have normal cell cycle regulation is of great significance. The pathogenesis of related molecular markers of BRAF gene is the most important regulation of cell cycle and DEPDC1 protein in papillary thyroid carcinoma and thyroid papillary carcinoma of thyroid papillary carcinoma. Objective: To study the expression of DEPDC1 in papillary thyroid carcinoma and normal thyroid tissues adjacent to tumor in the study of wild type BRAF gene in papillary thyroid papillary carcinoma in tumor tissue and BRAF gene mutation between the expression of DEPDC1 type papillary thyroid carcinoma tissues, and DEPDC1 analysis The relationship between papillary thyroid carcinoma and BRAF gene mutation and the clinical features. To study whether DEPDC1 can be used in clinical diagnosis and treatment of papillary thyroid carcinoma and provide experimental basis. Methods: a comparative study on clinical samples of hospital based by the method of quasi applications of molecular epidemiology, and make pathological tissue protein extraction by using the existing specimens. The expression of DEPDC1 was detected by immunohistochemistry method in papillary thyroid cancer tissues and normal thyroid tissues adjacent to tumor site. By immunoblotting detection of thyroid papillary carcinoma tumor tissue and tumor adjacent normal thyroid tissue, tumor tissue of wild type BRAF gene and BRAF gene mutation in tumor tissues, DEPDC1 expression different clinical features of papillary thyroid carcinoma group. Results: immunohistochemistry results showed that DEPDC1 in papillary thyroid carcinoma Expression and tumor adjacent normal tissues. In 5 cases of pathological sections of tumor tissues were detected in 1 cases of negative expression, 4 cases were strongly positive, 2 cases of tumor adjacent normal tissues were detected by weak positive expression of.DEPDC1 protein was localized in the nucleus and cytoplasm. The results of Western blot showed that the expression of DEPDC1 protein in papillary thyroid carcinoma in case (59 (14) 62), the results of Western blot showed that DEPDC1 protein in tumor tissues for expression (14 (14) 20). The results of Western blot showed that the expression of DEPDC1 protein in papillary thyroid carcinoma was (1.60 + 0.82), significantly higher than that of DEPDC1 protein in tumor adjacent normal expression the amount of thyroid tissue (0.58 + 0.19) the difference was statistically significant (P0.05) expression of mutant.DEPDC1 protein in tumor tissue was in the BRAF gene (1.83 + 0.80), was significantly higher than that of wild type BRAF gene expression in tumor tissue (1.03 + 0.45) difference Statistical significance (P0.05). The expression of DEPDC1 protein were male patients and female patients in tumor tissues (1.41 + 0.71), (1.64 + 0.83) the difference was not statistically significant (P0.05). Older than 45 years and less than the amount of respectively the expression of DEPDC1 protein in tumor tissue of 45 (1.51 + 0.67 (1.64 + 0.91)), the difference was not statistically significant (P0.05). The experimental results showed that DEPDC1 protein could be detected in the presence of papillary thyroid carcinoma and tumor adjacent normal tissues, expression intensity was significantly higher than that of tumor adjacent normal thyroid tissues and tumor tissues, specific molecular markers for sudden the mutant BRAF gene positive expression of DEPDC1 protein and the degree of papillary thyroid carcinoma, and the expression of DEPDC1 protein was associated with gender, clinical features of age. Conclusion: the localization of DEPDC1 protein in thyroid papillary carcinoma cell and nucleus In the cytoplasm, the expression of DEPDC1 is positively correlated with the thyroid papillary carcinoma and the mutation of the BRAF gene, and is not related to the sex and age.

【学位授予单位】：青岛大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R736.1

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