本文關(guān)鍵詞： 甲狀腺癌 基因突變 過氧化物酶增殖物激活受體-γ 鈉碘轉(zhuǎn)運體 促甲狀腺激素受體　出處：《蘭州大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：目的:探討分化型甲狀腺癌(DTC)鼠類肉瘤濾過性毒菌致癌同源體B1(BRAF)基因突變、端粒酶逆轉(zhuǎn)錄酶(TERT)啟動子突變和過氧化物酶增殖物激活受體γ(PPARγ)、鈉碘轉(zhuǎn)運體(NIS)及促甲狀腺激素受體(TSHR)表達(dá)及臨床意義,并研究BRAF基因突變、TERT啟動子突變對PPARγ、NIS及TSHR表達(dá)的影響及相關(guān)性。方法:收集病理確診的DTC患者229例,并取同期手術(shù)治療的結(jié)節(jié)性甲狀腺腫52例及正常甲狀腺組織31例。提取DNA采用PCR擴增產(chǎn)物直接測序法檢測BRAF基因V600E點突變、TERT啟動子C228T及C250T點突變,免疫組織化學(xué)SP法檢測PPARγ、NIS及TSHR蛋白表達(dá)。采用SPSS 22.0統(tǒng)計軟件Pearson chi-square(χ2)分析和非參數(shù)Spearman相關(guān)分析,P0.05為差異有統(tǒng)計學(xué)意義。結(jié)果:1.結(jié)節(jié)性甲狀腺腫及正常甲狀腺組織中均未發(fā)現(xiàn)BRAF V600E基因突變和TERT啟動子C228T及C250T點突變。2.DTC患者BRAF V600E基因突變率為62.0%,與性別、年齡、腫瘤大小、淋巴結(jié)轉(zhuǎn)移及復(fù)發(fā)危險度分層均無關(guān)(P0.05)。3.DTC患者TERT啟動子突變率為7.9%,其中C250T位點突變率為7.0%,C228T位點為0.9%,與性別、年齡及復(fù)發(fā)危險度分層相關(guān)(P0.05)。4.DTC患者TERT啟動子突變同時伴BRAF V600E基因突變率為61.1%,與淋巴結(jié)轉(zhuǎn)移及復(fù)發(fā)危險度分層相關(guān)(P0.05)。5.DTC患者BRAF V600E突變組PPARγ陽性率為59.9%,高于BRAF V600E野生組26.4%(P0.05);DTC患者PPARγ陽性率在只存在BRAF V600E突變組(BRAF+、TERT-)和BRAF V600E、TERT啟動子同時突變組(BRAF+、TERT+)分別為59.5%和63.6%,均高于BRAF V600E、TERT啟動子均未突變組(BRAF-、TERT-)25.0%(P0.05)。6.NIS在DTC中陽性率為55.5%,低于結(jié)節(jié)性甲狀腺腫78.9%及正常甲狀腺組織77.4%(P0.05);DTC患者BRAF+、TERT+組NIS陽性率18.2%,低于BRAF-、TERT-組51.3%(P0.05);DTC患者NIS細(xì)胞漿表達(dá)者48.2%發(fā)生于BRAF V600E突變組高于BRAF V600E野生組29.5%;細(xì)胞膜表達(dá)者70.5%發(fā)生于BRAF V600E野生組高于BRAF V600E突變組51.8%(P0.05)。7.TSHR在DTC中陽性率為41.0%,與腫瘤大小有關(guān)(P0.05);DTC患者BRAF V600E突變組TSHR陽性率48.6%高于BRAF V600E野生組28.7%(P0.05);DTC患者TSHR陽性率在BRAF+、TERT-組,BRAF-、TERT+組及BRAF+、TERT+組分別為46.6%、85.7%、72.7%,均高于BRAF-、TERT-組23.8%(P0.05)。結(jié)論:1.檢測BRAF V600E基因突變和TERT啟動子C228T及C250T點突變有助于鑒別甲狀腺腫瘤良、惡性。2.DTC患者BRAF V600E基因突變率較高,但單獨檢測BRAF V600E突變尚難對DTC預(yù)后評估有指導(dǎo)。TERT啟動子在DTC中突變率較低,且以C250T位點突變更多見。聯(lián)合檢測BRAF V600E和TERT啟動子突變對DTC預(yù)后評估具有指導(dǎo)意義。3.DTC患者PPARγ表達(dá)受BRAF V600E和TERT啟動子突變共同影響,提示BRAF V600E和TERT啟動子突變可能與PPARγ共同作用促進(jìn)腫瘤組織增生,支持PPARγ作為促癌因子的觀點。4.DTC患者NIS表達(dá)定位與BRAF V600E有關(guān),NIS表達(dá)降低與BRAF V600E和TERT啟動子同時突變有關(guān),檢測BRAF V600E和TERT啟動子同時突變可間接預(yù)測DTC組織的攝碘能力。5.DTC患者TSHR表達(dá)受BRAF V600E和TERT啟動子突變共同影響。
[Abstract]:Objective: to investigate the mutation of the oncogenic homologue B1BRAF of murine sarcomas derived from differentiated thyroid carcinoma (DTC). Expression and clinical significance of telomerase reverse transcriptase promoter mutation and peroxidase proliferator activated receptor 緯 PPAR 緯, sodium iodide transporter (NIS) and thyrotropin receptor (TSH). To study the effect and correlation of BRAF gene mutation and TERT promoter mutation on the expression of PPAR 緯 -NIS and TSHR. Methods: 229 patients with pathologically diagnosed DTC were collected. DNA was extracted from 52 cases of nodular goiter and 31 cases of normal thyroid tissue in the same period of operation. PCR amplification products were used to detect C228T and C250T point mutations in the promoter of BRAF gene V600E site-mutation, C228T and C250T, respectively. Immunohistochemical SP method was used to detect the expression of PPAR 緯 nis and TSHR protein. There was significant difference between SPSS 22.0 statistical software Pearson chi-square (蠂 2) and nonparametric Spearman correlation analysis (P0.05). Results: 1. Nodular goiter and normal thyroid tissue were all different. No mutation of BRAF V600E gene and point mutation of C228T and C250T of TERT promoter. 2. The mutation rate of BRAF V600E gene in patients with DTC was 62.0%, which was related to sex. Age, tumor size, lymph node metastasis and recurrence risk stratification were not correlated with the mutation rate of TERT promoter in DTC patients. The mutation rate of C250T locus was 7.0T and C228T locus was 0.9g with sex. The mutation rate of TERT promoter with BRAF V600E gene was 61.1in patients with age and recurrence risk stratification. The positive rate of PPAR 緯 in BRAF V600E mutation group was 59.9in patients with BRAF V600E mutation, which was higher than that in wild BRAF V600E group, which was associated with lymph node metastasis and recurrence risk stratification (P 0.05). 5. The positive rate of PPAR 緯 in BRAF V600E mutation group was higher than that in BRAF V600E wild group. The positive rate of PPAR 緯 in BRAF V600E mutation group and BRAF V600Etert promoter mutation group was 59.5% and 63.6, respectively, which was higher than that in BRAF V600 Etert promoter non-mutation group, BRAF-TERT promoter with no mutation, BRAF-TERT positive rate in DTC was 55.5, which was lower than that in nodular goiter 78.9%. The positive rate of NIS in the BRAF group was 18.2and was lower than that in the BRAF-TERT- group, which was lower than that in the BRAF V600E mutation group and the BRAF V600E wild group. The expression rate of NIS in the BRAF V600E mutation group was higher than that in the BRAF V600E wild group, and the cell membrane expression rate in the BRAF V600E wild group was higher than that in the BRAF V600E process. The positive rate of TSHR in the BRAF V600E mutation group was 48.6% higher than that in the BRAF V600E mutant group, and the TSHR positive rate in BRAF TERT- group BRAF-TERT group and BRAF tert group was 46.60.75.72.70.The positive rate of TSHR was higher than that of BRAF-T- group 23.8TERP0.052.72.70.The positive rate of TSHR in BRAF TERT- group was higher than that in BRAF V600E mutant group (28.75.72.72.72.77.The positive rate of TSHR in BRAF TERT- group BRAF-TERT group and BRAF tert group was 46.65.72.72.77.The positive rate of TSHR in BRAF V600E mutation group was higher than that in BRAF V600E wild group 28.75.72.72.71.Conclusion:. The mutation of BRAF V600E gene and the point mutation of C228T and C250T promoter of TERT are helpful in differentiating benign thyroid tumors. 2.The mutation rate of BRAF V600E gene in DTC patients was high, but it was difficult to evaluate the prognosis of DTC by detecting BRAF V600E mutation alone. The mutation rate of TERT promoter was lower in DTC. The combined detection of BRAF V600E and TERT promoter mutations may be helpful in evaluating the prognosis of DTC. 3. The expression of PPAR 緯 in DTC patients is affected by BRAF V600E and TERT promoter mutations. The results suggest that the mutation of BRAF V600E and TERT promoter may promote the proliferation of tumor tissue together with PPAR 緯. The view that PPAR 緯 is used as a carcinogenic factor. 4. The location of NIS expression in DTC patients is related to the decrease of BRAF V600E expression and the simultaneous mutation of BRAF V600E and TERT promoter. Detection of simultaneous mutations in BRAF V600E and TERT promoters could indirectly predict the iodine uptake ability of DTC tissues. 5. TSHR expression in DTC patients was affected by both BRAF V600E and TERT promoter mutations.
【學(xué)位授予單位】：蘭州大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R736.1

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