国际免疫学杂志
國際免疫學雜誌
국제면역학잡지
INTERNATIONAL JOURNAL OF IMMUNOLOGY
2013年
2期
162-166
,共5页
高月秋%曲波%刘波%任磊
高月鞦%麯波%劉波%任磊
고월추%곡파%류파%임뢰
6-氧-甲基鸟嘌呤-DNA甲基转移酶%CpG岛%DNA甲基化%表型遗传改变
6-氧-甲基鳥嘌呤-DNA甲基轉移酶%CpG島%DNA甲基化%錶型遺傳改變
6-양-갑기조표령-DNA갑기전이매%CpG도%DNA갑기화%표형유전개변
O6-methylguanine-DNA%methyltransferase%CpG island%DNA methylation%Phenotypic genetic change
目的 验证6-氧-甲基鸟嘌呤-DNA甲基转移酶(MGMT)基因启动子CpG岛高甲基化在结直肠癌发生、发展中的作用,并探讨联合检测基因甲基化发现早期结直肠肿瘤的可能性.方法 用甲基特异性PCR(MSP)检测20例正常大肠粘膜、32例散发性结直肠腺瘤和34例散发性结直肠腺癌组织DNA中MGMT基因启动子的甲基化状况.同时用免疫组化方法检测MGMT蛋白的表达情况.结果 正常大肠粘膜组织均不存在甲基化,40.6％ (13/32)的腺瘤组织和44.1％ (15/34)的腺癌组织存在MGMT基因启动子CpG岛高甲基化.正常大肠黏膜胞核和胞浆表达MGMT蛋白,21.9％ (7/32)的腺瘤和50.0％ (17/34)的腺癌MGMT蛋白表达缺失,其差异有统计学意义(P=0.018).7例MGMT表达缺失的腺瘤中6例存在甲基化(P=0.027),17例表达缺失的腺癌中14例存在甲基化(x2=17,P＜0.001).结论 结直肠肿瘤中存在高频率MGMT基因启动子CpG岛高甲基化和MGMT蛋白表达缺失,腺癌中蛋白表达缺失比腺瘤中更常见.MGMT基因表型遗传性失活可能在结直肠肿瘤发生过程中起重要作用,且联合检测异常甲基化基因可能为结直肠肿瘤的早期发现提供帮助.
目的 驗證6-氧-甲基鳥嘌呤-DNA甲基轉移酶(MGMT)基因啟動子CpG島高甲基化在結直腸癌髮生、髮展中的作用,併探討聯閤檢測基因甲基化髮現早期結直腸腫瘤的可能性.方法 用甲基特異性PCR(MSP)檢測20例正常大腸粘膜、32例散髮性結直腸腺瘤和34例散髮性結直腸腺癌組織DNA中MGMT基因啟動子的甲基化狀況.同時用免疫組化方法檢測MGMT蛋白的錶達情況.結果 正常大腸粘膜組織均不存在甲基化,40.6％ (13/32)的腺瘤組織和44.1％ (15/34)的腺癌組織存在MGMT基因啟動子CpG島高甲基化.正常大腸黏膜胞覈和胞漿錶達MGMT蛋白,21.9％ (7/32)的腺瘤和50.0％ (17/34)的腺癌MGMT蛋白錶達缺失,其差異有統計學意義(P=0.018).7例MGMT錶達缺失的腺瘤中6例存在甲基化(P=0.027),17例錶達缺失的腺癌中14例存在甲基化(x2=17,P＜0.001).結論 結直腸腫瘤中存在高頻率MGMT基因啟動子CpG島高甲基化和MGMT蛋白錶達缺失,腺癌中蛋白錶達缺失比腺瘤中更常見.MGMT基因錶型遺傳性失活可能在結直腸腫瘤髮生過程中起重要作用,且聯閤檢測異常甲基化基因可能為結直腸腫瘤的早期髮現提供幫助.
목적 험증6-양-갑기조표령-DNA갑기전이매(MGMT)기인계동자CpG도고갑기화재결직장암발생、발전중적작용,병탐토연합검측기인갑기화발현조기결직장종류적가능성.방법 용갑기특이성PCR(MSP)검측20례정상대장점막、32례산발성결직장선류화34례산발성결직장선암조직DNA중MGMT기인계동자적갑기화상황.동시용면역조화방법검측MGMT단백적표체정황.결과 정상대장점막조직균불존재갑기화,40.6％ (13/32)적선류조직화44.1％ (15/34)적선암조직존재MGMT기인계동자CpG도고갑기화.정상대장점막포핵화포장표체MGMT단백,21.9％ (7/32)적선류화50.0％ (17/34)적선암MGMT단백표체결실,기차이유통계학의의(P=0.018).7례MGMT표체결실적선류중6례존재갑기화(P=0.027),17례표체결실적선암중14례존재갑기화(x2=17,P＜0.001).결론 결직장종류중존재고빈솔MGMT기인계동자CpG도고갑기화화MGMT단백표체결실,선암중단백표체결실비선류중경상견.MGMT기인표형유전성실활가능재결직장종류발생과정중기중요작용,차연합검측이상갑기화기인가능위결직장종류적조기발현제공방조.
Objective To verify the effect of promoter hypermethylation of O6-methylguanine-DNA methyltransferase(MGMT) gene on colorectal tumorigenesis and progression,and to explore the possibility of find the early colorectal cancer by joint detection of gene methylation.Methods The promoter hypermethylation status of O6-methylguanine-DNA methyltransferase gene was assayed in 32 sporadic colorectal adenomas,34 sporadic colorectal carcinomas and 20 normal colorectal mucosa tissues by methylation-specific PCR.,The expression of MGMT protein in the same batch of samples was detected with immunohistochemistry as well.Results No CpG land hypermethylation was found in the normal colorectal mucosa tissues,but in 40.6％ (13/32) of adenomas and 44.1％ (15/34) of carcinomas,it was confirmed.Compared with the MGMT proteins expression in nucleus and cytoplasm of normal colorectal mucosa tissues.the loss of MGMT expression was verified in 21.9％ (7/32) of adenomas and 50.0％ (17/34) of carcinomas,respectively.There were significant difference among them (P =0.018).On the other hand,because of the salient overlapping phenomenon,i.e.methylation in 6 of the 7 adenomas (P =0.027) and 14 of the 17 caronomas(x2 =17,P ＜ 0.001) with MGMT expression losing was discovered,the high relationship between the CpG island methylation and MGMT protein losing was proofed.Conclusions Promoter hypermethylation and loss of expression of MGMT gene was common events in colorectal tumorigenesis,and loss of expression of MGMT occurs more frequently in carcinoma than in adenoma in sporadic patients.It suggests that epigenetic inactivation of MGMT plays an important role in colorectal tumorigenesis,and it may be can provide a help for find the early colorectal cancer by joint detection of gene methylation.
