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抑癌基因INPP4B和PTEN在结节性甲状腺疾病组织中的蛋白表达及其意义

发布时间:2018-07-27 16:48
【摘要】:目的:通过免疫组织化学法检测抑癌基因INPP4B和PTEN在正常甲状腺组织以及结节性甲状腺疾病组织中的表达,结合疾病组织的病理学特征,探讨两者在结节性甲状腺疾病发生发展中的作用及临床意义,以期为甲状腺肿瘤寻找新的标记物,同时也为开发分子靶向药物提供理论依据。方法:收集川北医学院附属医院2014年7月1日至2016年6月1日期间诊断明确并经病理分型的结节性甲状腺疾病组织样本134例,其中结节性甲状腺肿41例,甲状腺腺瘤45例,甲状腺癌48例(乳头状癌43例,滤泡状癌3例,未分化癌1例,髓样癌1例),正常甲状腺组织20例,应用免疫组织化学法检测抑癌基因INPP4B和PTEN的表达情况。运用SPSS13.0统计学软件进行数据分析,双侧检验,α=0.05为检验水准,P0.05为差异有统计学意义;INPP4B和PTEN的蛋白表达在不同病理类型甲状腺结节中的相关性采用Spearman等级相关分析;INPP4B和PTEN在正常组织、结节性甲状腺肿、甲状腺腺瘤及甲状腺癌中的表达差异及与不同临床病理特征的关系采用χ2检验进行分析。结果:(1)在甲状腺癌组织、甲状腺腺瘤组织、结节性甲状腺肿组织、正常组织中,INPP4B基因的蛋白表达呈递增趋势,但INPP4B基因在正常组织、结节性甲状腺肿组织、甲状腺腺瘤组织中的蛋白表达水平不具有显著性差异(p0.05)。INPP4B基因在甲状腺癌组织中的蛋白表达水平明显降低,与良性结节性甲状腺疾病组织以及正常甲状腺组织比较,差异有统计学意义(p0.05)。(2)在甲状腺癌组织、甲状腺腺瘤组织、结节性甲状腺肿组织、正常组织中,pten基因的蛋白表达呈递增趋势,但pten基因在正常组织、结节性甲状腺肿组织、甲状腺腺瘤组织中的蛋白表达水平不具有显著性差异(p0.05)。pten基因在甲状腺癌组织中的蛋白表达水平明显降低,与良性结节性甲状腺疾病组织以及正常甲状腺组织比较,差异有统计学意义(p0.05)。(3)inpp4b和pten基因在结节性甲状腺肿组织和甲状腺腺瘤组织中的蛋白表达与患者的年龄、性别、结节大小、钙化灶没有相关性(p0.05)。(4)inpp4b基因在甲状腺癌组织中的蛋白表达与患者的性别、结节大小、钙化灶、颈部淋巴结转移相关,女性患者、2cm结节、有钙化灶、伴颈部淋巴结转移的组织inpp4b蛋白表达显著低于男性患者、≤2cm结节、无钙化灶、不伴颈部淋巴结转移的组织,差异有统计学意义(p0.05),与年龄没有相关性(p0.05)。(5)pten基因在甲状腺癌组织中的蛋白表达与钙化灶、颈部淋巴结转移相关,有钙化灶、伴颈部淋巴结转移的组织pten蛋白表达显著低于无钙化灶、不伴颈部淋巴结转移的组织,差异有统计学意义(p0.05),与年龄、性别、结节大小没有相关性(p0.05)。(6)在结节性甲状腺肿、甲状腺腺瘤及甲状腺癌组织中inpp4b和pten基因的蛋白表达均呈正相关,有统计学意义(rs=0.396,p0.05;rs=0.448,p0.05;rs=0.904,p0.05)。结论:(1)inpp4b和pten基因在甲状腺癌组织、甲状腺腺瘤组织、结节性甲状腺肿组织、正常甲状腺组织中的蛋白表达水平依次升高。(2)INPP4B和PTEN基因在甲状腺癌组织中的蛋白表达明显降低,可以作为鉴别甲状腺结节良恶性的潜在参考指标。(3)INPP4B和PTEN基因的低表达可能与甲状腺癌的发生发展及颈部淋巴结转移密切相关。(4)INPP4B和PTEN基因的蛋白表达具有相关性,在甲状腺癌的发生发展中具有协同作用。(5)INPP4B基因的蛋白表达提示与性别相关,可能是甲状腺癌男女发病率存在差异的潜在原因之一。
[Abstract]:Objective: to detect the expression of tumor suppressor gene INPP4B and PTEN in normal thyroid tissue and nodular thyroid diseases by immunohistochemistry, and to explore the role and clinical significance of the two genes in the development of nodular thyroid diseases in order to find new markers for thyroid tumor. At the same time, we also provide a theoretical basis for the development of molecular targeted drugs. Methods: 134 cases of nodular thyroid diseases were collected from July 1, 2014 to June 1, 2016 in Affiliated Hospital of Chuanbei Medical College, including 41 cases of nodular goiter, 45 cases of thyroid adenoma, 48 cases of thyroid carcinoma (43 papillary carcinoma). 3 cases of follicular carcinoma, 1 cases of undifferentiated carcinoma, 1 cases of medullary carcinoma and 20 cases of normal thyroid tissue, the expression of tumor suppressor gene INPP4B and PTEN was detected by immunohistochemistry. SPSS13.0 statistics software was used for data analysis, bilateral test, and alpha =0.05 as the test level, P0.05 was statistically significant; the protein expression of INPP4B and PTEN was expressed. Spearman correlation analysis was used in different pathological types of thyroid nodules; the expression difference between INPP4B and PTEN in normal tissue, nodular goiter, thyroid adenoma and thyroid carcinoma and the relationship with different clinicopathological features were analyzed by chi 2 test. Results: (1) thyroid adenoma and thyroid adenoma In tissue, nodular goiter tissue and normal tissue, the protein expression of INPP4B gene is increasing, but the protein expression level of INPP4B gene in normal tissue, nodular goiter tissue and thyroid adenoma has no significant difference (P0.05).INPP4B based protein expression in thyroid cancer tissue is significantly reduced. Compared with benign nodular thyroid tissue and normal thyroid tissue, the difference was statistically significant (P0.05). (2) the protein expression of PTEN gene in thyroid carcinoma tissue, thyroid adenomatous tissue, nodular goiter tissue and normal tissue increased, but the PTEN gene was in normal tissue, nodular goiter tissue, and a There was no significant difference in the protein expression level in the adenoma tissue (P0.05), the protein expression level of.Pten gene in thyroid carcinoma tissue was significantly reduced, and compared with the benign nodular thyroid tissue and normal thyroid tissue, the difference was statistically significant (P0.05). (3) the inpp4b and PTEN genes were in the nodular goiter tissue The protein expression in the thyroid adenoma was not associated with age, sex, nodule size and calcification (P0.05). (4) the protein expression of inpp4b gene in thyroid carcinoma tissues was associated with the sex, size of nodules, calcification, neck lymph node metastasis, female patients, 2cm nodules, calcified foci, and cervical lymph node metastasis. The expression of inpp4b protein in tissue was significantly lower than that of male patients, less than 2cm nodules, no calcification, no cervical lymph node metastasis, there was significant difference (P0.05) and no correlation with age (P0.05). (5) the protein expression of PTEN gene in thyroid cancer tissues was associated with calcification, neck lymph node metastasis, calcification, neck lymph node metastasis. The expression of PTEN protein in the metastatic tissue was significantly lower than that without calcification, without cervical lymph node metastasis. The difference was statistically significant (P0.05). There was no correlation with age, sex, and nodule size (P0.05). (6) the protein expression of inpp4b and PTEN genes in nodular goiter, thyroid adenoma and thyroid cancer tissues were positively correlated There were statistical significance (rs=0.396, P0.05; rs=0.448, P0.05; rs=0.904, P0.05). Conclusion: (1) the protein expression levels of inpp4b and PTEN genes in thyroid carcinoma tissue, thyroid adenoma, nodular goiter tissue and normal thyroid tissue are increased in turn. (2) the protein expression of INPP4B and PTEN genes in thyroid cancer tissues is significantly reduced. It can be used as a potential reference for differentiating benign and malignant thyroid nodules. (3) the low expression of INPP4B and PTEN genes may be closely related to the development of thyroid carcinoma and cervical lymph node metastasis. (4) the protein expression of INPP4B and PTEN genes is related, and has synergistic effect in the development of thyroid cancer. (5) the egg of the INPP4B gene White expression is associated with sex. It may be one of the potential reasons for the difference in incidence of thyroid cancer between men and women.
【学位授予单位】:川北医学院
【学位级别】:硕士
【学位授予年份】:2017
【分类号】:R581;R736.1

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