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Correlation Among BRAF Gene Mutation,TERT Promoter Mutation And Expression Of PPAR??NIS?TSHR In Differentiated Thyroid Carcinoma

Posted on:2018-09-08Degree:MasterType:Thesis
Country:ChinaCandidate:X T RuFull Text:PDF
GTID:2334330533457764Subject:biology
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Objective: To investigate v-raf murine sarcoma viral oncogene homolog B1(BRAF)gene mutation,telomerase reverse transcriptase(TERT)promoter mutation and expression of peroxisome proliferator activated receptor ?(PPAR?),sodium iodide symporter(NIS),thyroid stimulating hormone receptor(TSHR)and clinical significance,to explore the correlation among BRAF V600 E,TERT promoter mutation and expression of PPAR?,NIS,TSHR in differentiated thyroid carcinoma(DTC).Methods: The 229 cases of pathologic confirmed DTC,52 cases of nodular goiter,31 cases of normal thyroid tissue were collected.BRAF V600 E and TERT promoter mutations were detected by direct sequencing after extracting DNA,Immunohistochemistry staining was used to detect the expression of PPAR?,NIS,TSHR.The SPSS 22.0 statistical software Pearson chi-square(?2)and Nonparametric Spearman Correlation Analysis was used to analysis,P<0.05 for the difference was statistically significant.Results:1.BRAF V600 E gene mutation and TERT promoter(C228T and C250T)mutation were not found in nodular goiter and normal thyroid tissue.2.The mutation rate of BRAF V600 E was 62.0% in patients with DTC,it was not associated with gender,age,tumor size,lymph node metastasis and recurrence risk stratification(P>0.05).3.The mutation rate of TERT promoter was 7.9% in patients with DTC which including C250 T 7.0% and C228 T 0.9%,it was associated with gender,age and recurrence risk stratification(P<0.05).4.The mutation rate of TERT promoter mutation also harbored the BRAF V600 E mutation was 61.1% in patients with DTC,they were associated with lymph node metastasis and recurrence risk stratification(P<0.05).5.The positive rate of PPAR? in BRAF V600 E mutation group(59.9%)was higher than BRAF V600 E wild-type group(26.4%)(P<0.05)in patients with DTC;The positive rate of PPAR? in only BRAF V600 E mutation group(BRAF+?TERT-)and simultaneous BRAF V600 E and TERT promoter mutations group(BRAF+?TERT+)were 59.5% and 63.6% respectively in patients with DTC,they were higher than none of BRAF V600 E and TERT promoter mutation group(BRAF-?TERT-)(25.0%)(P< 0.05).6.The positive rate of NIS in DTC was 55.5%,it was lower than nodular goiter(78.9%)and normal thyroid tissue(77.4%)(P<0.05);The positive rate of NIS in BRAF+,TERT+ group was 18.2% in patients with DTC,it was lower than BRAF-?TERT-group(51.3%)(P<0.05);In patients with DTC,the cytoplasmic expression rate of NIS was 48.2% in BRAF V600 E mutation group,it was higher than BRAF V600 E wild-type group(29.5%),the membrane expression rate of NIS was 70.5% in BRAF V600 E wild-type group,it was higher than BRAF V600 E mutation group(51.8%)(P<0.05).7.The positive rate of TSHR in DTC was 41.0%,it was associated with tumor size(P<0.05);The positive rate of TSHR in BRAF V600 E mutation group(48.6%)was higher than BRAF V600 E wild-type group(28.7%)(P<0.05)in patients with DTC;The positive rate of TSHR in BRAF+?TERT-group,BRAF-?TERT+ group,BRAF+?TERT+ group was 46.6%?85.7%?72.7% respectively,they were higher than BRAF-?TERT-group(23.8%)(P<0.05)in patients with DTC.Conclusion: 1.Detection of BRAF V600 E gene mutation and TERT promoter(C228T and C250T)mutation can help to identify benign and malignant thyroid tumors.2.BRAF V600 E has a high mutation rate in patients with DTC,but it is difficult to instructive prognosis assessment for DTC by detect BRAF V600 E mutation individually.TERT promoter has a low mutation rate in patients with DTC,and the C250 T was more common.The detection of BRAF V600 E combination with TERT promoter mutation is instructive to prognosis assessment of patients with DTC.3.PPAR? expression was affected by BRAF V600 E and TERT promoter mutations in patients with DTC,suggesting that BRAF V600 E and TERT promoter mutations may interact with PPAR? to promote tumor tissue hyperplasia,support that PPAR? as a carcinogenic factor.4.NIS expression location was associated with BRAF V600 E mutation in patients with DTC,NIS expression decreased in DTC was associated with simultaneous BRAF V600 E and TERT promoter mutations,Detection of simultaneous BRAF V600 E and TERT promoter mutations can predict the iodine capacity of DTC tissue.5.TSHR expression was affected by BRAF V600 E and TERT promoter mutations in patients with DTC.
Keywords/Search Tags:Thyroid carcinoma, Gene mutation, Peroxisome proliferator activated receptor ?, Sodium iodide symporter, Thyroid stimulating hormone receptor
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