CAJ | 학술논문

目的：探讨青少年甲状腺乳头状癌(PTC)肿瘤抑制候选基因1(TUSC1)基因启动子区域的甲基化状态及其与蛋白表达的相关性。方法选择40例青少年PTC及其对应的癌旁组织,分别取自2010年7月至2013年12月郑州大学第一附属医院甲状腺手术标本,均经病理证实。男12例,女28例；中位年龄14(10~18)岁。肿瘤淋巴结转移(TNM)分期Ⅰ~Ⅱ期13例,Ⅲ~Ⅳ期27例；病理分级Ⅰ级15例,Ⅱ级25例；淋巴结转移22例阳性,18例阴性。运用甲基化特异性聚合酶链反应(MSP)检测40例青少年PTC及其对应的癌旁组织中TUSC1启动子甲基化状态；采用 Western blot法检测 TUSC1蛋白的表达。结果40例青少年 PTC中, TUSC1启动子区出现甲基化的有24例(60%,24/40例),在对应的癌旁组织中均未出现基因甲基化(0),二者比较差异有统计学意义(χ2=34.28,P<0.05)。青少年PTC中TUSC1启动子甲基化与TNM分期、病理分级及淋巴结转移有关(χ2=4.862、7.111、5.625,P均<0.05)。 TUSC1蛋白表达的有12例(30%,12/40例),在对应的癌旁组织中均出现TUSC1蛋白的表达(100%),二者比较差异有统计学意义(χ2=14.118,P<0.05)。青少年PTC中TUSC1蛋白的表达与TNM分期、病理分级及淋巴结转移有关(χ2=5.215、6.222、5.079,P均<0．05)。TUSC1启动子甲基化与蛋白表达呈负相关(r=-0.84,P<0．05)。结论 TUSC1启动子甲基化是基因失活的重要机制之一,TUSC1蛋白的表达与TNM分期、病理分级及淋巴结转移有关,在青少年PTC的发生及发展中起重要作用。
목적：탐토청소년갑상선유두상암(PTC)종류억제후선기인1(TUSC1)기인계동자구역적갑기화상태급기여단백표체적상관성。방법선택40례청소년PTC급기대응적암방조직,분별취자2010년7월지2013년12월정주대학제일부속의원갑상선수술표본,균경병리증실。남12례,녀28례；중위년령14(10~18)세。종류림파결전이(TNM)분기Ⅰ~Ⅱ기13례,Ⅲ~Ⅳ기27례；병리분급Ⅰ급15례,Ⅱ급25례；림파결전이22례양성,18례음성。운용갑기화특이성취합매련반응(MSP)검측40례청소년PTC급기대응적암방조직중TUSC1계동자갑기화상태；채용 Western blot법검측 TUSC1단백적표체。결과40례청소년 PTC중, TUSC1계동자구출현갑기화적유24례(60%,24/40례),재대응적암방조직중균미출현기인갑기화(0),이자비교차이유통계학의의(χ2=34.28,P<0.05)。청소년PTC중TUSC1계동자갑기화여TNM분기、병리분급급림파결전이유관(χ2=4.862、7.111、5.625,P균<0.05)。 TUSC1단백표체적유12례(30%,12/40례),재대응적암방조직중균출현TUSC1단백적표체(100%),이자비교차이유통계학의의(χ2=14.118,P<0.05)。청소년PTC중TUSC1단백적표체여TNM분기、병리분급급림파결전이유관(χ2=5.215、6.222、5.079,P균<0．05)。TUSC1계동자갑기화여단백표체정부상관(r=-0.84,P<0．05)。결론 TUSC1계동자갑기화시기인실활적중요궤제지일,TUSC1단백적표체여TNM분기、병리분급급림파결전이유관,재청소년PTC적발생급발전중기중요작용。
Objective To study the relationship between status of methylation of tumor suppressor candidate 1 gene(TUSC1) promoter and expression of its protein in adolescent papillary thyroid carcinoma(PTC). Methods Forty cases of adolescent PTC were chosen and the corresponding para carcinoma tissues were taken from July 2010 to Decem-ber 2013 in the First Affiliated Hospital of Zhengzhou University surgical specimens of the thyroid gland and were con-firmed by pathology. Male 12 cases,female 28 cases,median age 14 (10-18) years old. Tumor node metastasis (TNM) stageⅠ-Ⅱ13 cases,Ⅲ-Ⅳstage 27 cases;gradeⅠin 15 cases,gradeⅡin 25 cases;lymph node metastasis in 22 cases,18 cases were negative. Methylation-specific polymerase chain reaction (MSP) and Western blot were applied respectively to examine the methyaltion of TUSC1 gene promoter and its protein expression of 40 samples of adolescent PTC and their matched adjacent non-cancerous epithelium. Results The results of MSP revealed that there was no methylation of TUSC1 gene promoter in adjacent non-cancerous epithelium,while in the adolescent PTC,the hyper-methylation rate was 60%(24/60 cases,χ2=34. 28,P<0. 05). In additional,it was related to the TNM stage,pathological grade and lymph node metastasis (χ2=4. 862,7. 111,5. 625,all P<0. 05). The result of Western blot revealed that the positive expression rate of TUSC1 protein was 100% in adjacent non-cancerous epithelium and 30%(12/40 cases) in adolescent PTC (χ2=14. 118,P<0. 05),which was related to the TNM stage,pathological grade and lymph node metastasis (χ2=5. 215,6. 222, 5. 079,all P<0. 05). There was distinct correlation between methylation of TUSC1 gene promoter and the protein expres-sion (r=-0. 84,P<0. 05). Conclusions Methylation of promoter might be one of the important mechanisms of inactiva-tion of TUSC1 gene,and might play an important role in carcinogenesis and progression of adolescent PTC.