發(fā)布時(shí)間：2018-07-27 16:48

【摘要】：目的:通過免疫組織化學(xué)法檢測抑癌基因INPP4B和PTEN在正常甲狀腺組織以及結(jié)節(jié)性甲狀腺疾病組織中的表達(dá),結(jié)合疾病組織的病理學(xué)特征,探討兩者在結(jié)節(jié)性甲狀腺疾病發(fā)生發(fā)展中的作用及臨床意義,以期為甲狀腺腫瘤尋找新的標(biāo)記物,同時(shí)也為開發(fā)分子靶向藥物提供理論依據(jù)。方法:收集川北醫(yī)學(xué)院附屬醫(yī)院2014年7月1日至2016年6月1日期間診斷明確并經(jīng)病理分型的結(jié)節(jié)性甲狀腺疾病組織樣本134例,其中結(jié)節(jié)性甲狀腺腫41例,甲狀腺腺瘤45例,甲狀腺癌48例(乳頭狀癌43例,濾泡狀癌3例,未分化癌1例,髓樣癌1例),正常甲狀腺組織20例,應(yīng)用免疫組織化學(xué)法檢測抑癌基因INPP4B和PTEN的表達(dá)情況。運(yùn)用SPSS13.0統(tǒng)計(jì)學(xué)軟件進(jìn)行數(shù)據(jù)分析,雙側(cè)檢驗(yàn),α=0.05為檢驗(yàn)水準(zhǔn),P0.05為差異有統(tǒng)計(jì)學(xué)意義;INPP4B和PTEN的蛋白表達(dá)在不同病理類型甲狀腺結(jié)節(jié)中的相關(guān)性采用Spearman等級相關(guān)分析;INPP4B和PTEN在正常組織、結(jié)節(jié)性甲狀腺腫、甲狀腺腺瘤及甲狀腺癌中的表達(dá)差異及與不同臨床病理特征的關(guān)系采用χ2檢驗(yàn)進(jìn)行分析。結(jié)果:(1)在甲狀腺癌組織、甲狀腺腺瘤組織、結(jié)節(jié)性甲狀腺腫組織、正常組織中,INPP4B基因的蛋白表達(dá)呈遞增趨勢,但I(xiàn)NPP4B基因在正常組織、結(jié)節(jié)性甲狀腺腫組織、甲狀腺腺瘤組織中的蛋白表達(dá)水平不具有顯著性差異(p0.05)。INPP4B基因在甲狀腺癌組織中的蛋白表達(dá)水平明顯降低,與良性結(jié)節(jié)性甲狀腺疾病組織以及正常甲狀腺組織比較,差異有統(tǒng)計(jì)學(xué)意義(p0.05)。(2)在甲狀腺癌組織、甲狀腺腺瘤組織、結(jié)節(jié)性甲狀腺腫組織、正常組織中,pten基因的蛋白表達(dá)呈遞增趨勢,但pten基因在正常組織、結(jié)節(jié)性甲狀腺腫組織、甲狀腺腺瘤組織中的蛋白表達(dá)水平不具有顯著性差異(p0.05)。pten基因在甲狀腺癌組織中的蛋白表達(dá)水平明顯降低,與良性結(jié)節(jié)性甲狀腺疾病組織以及正常甲狀腺組織比較,差異有統(tǒng)計(jì)學(xué)意義(p0.05)。(3)inpp4b和pten基因在結(jié)節(jié)性甲狀腺腫組織和甲狀腺腺瘤組織中的蛋白表達(dá)與患者的年齡、性別、結(jié)節(jié)大小、鈣化灶沒有相關(guān)性(p0.05)。(4)inpp4b基因在甲狀腺癌組織中的蛋白表達(dá)與患者的性別、結(jié)節(jié)大小、鈣化灶、頸部淋巴結(jié)轉(zhuǎn)移相關(guān),女性患者、2cm結(jié)節(jié)、有鈣化灶、伴頸部淋巴結(jié)轉(zhuǎn)移的組織inpp4b蛋白表達(dá)顯著低于男性患者、≤2cm結(jié)節(jié)、無鈣化灶、不伴頸部淋巴結(jié)轉(zhuǎn)移的組織,差異有統(tǒng)計(jì)學(xué)意義(p0.05),與年齡沒有相關(guān)性(p0.05)。(5)pten基因在甲狀腺癌組織中的蛋白表達(dá)與鈣化灶、頸部淋巴結(jié)轉(zhuǎn)移相關(guān),有鈣化灶、伴頸部淋巴結(jié)轉(zhuǎn)移的組織pten蛋白表達(dá)顯著低于無鈣化灶、不伴頸部淋巴結(jié)轉(zhuǎn)移的組織,差異有統(tǒng)計(jì)學(xué)意義(p0.05),與年齡、性別、結(jié)節(jié)大小沒有相關(guān)性(p0.05)。(6)在結(jié)節(jié)性甲狀腺腫、甲狀腺腺瘤及甲狀腺癌組織中inpp4b和pten基因的蛋白表達(dá)均呈正相關(guān),有統(tǒng)計(jì)學(xué)意義(rs=0.396,p0.05;rs=0.448,p0.05;rs=0.904,p0.05)。結(jié)論:(1)inpp4b和pten基因在甲狀腺癌組織、甲狀腺腺瘤組織、結(jié)節(jié)性甲狀腺腫組織、正常甲狀腺組織中的蛋白表達(dá)水平依次升高。(2)INPP4B和PTEN基因在甲狀腺癌組織中的蛋白表達(dá)明顯降低,可以作為鑒別甲狀腺結(jié)節(jié)良惡性的潛在參考指標(biāo)。(3)INPP4B和PTEN基因的低表達(dá)可能與甲狀腺癌的發(fā)生發(fā)展及頸部淋巴結(jié)轉(zhuǎn)移密切相關(guān)。(4)INPP4B和PTEN基因的蛋白表達(dá)具有相關(guān)性,在甲狀腺癌的發(fā)生發(fā)展中具有協(xié)同作用。(5)INPP4B基因的蛋白表達(dá)提示與性別相關(guān),可能是甲狀腺癌男女發(fā)病率存在差異的潛在原因之一。
[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.
【學(xué)位授予單位】：川北醫(yī)學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R581;R736.1

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