RUNX3、RASSF1A启动子高甲基化与胃癌进展转移的关系  

Correlations of RUNX3 and RASSF1A promoter hypermethylation with the progression and metastasis of gastric carcinoma

作　　者：林海[1] 曹俊[2] 张斌[2] 吴育美[2] 邹晓平[1,2] 

机构地区：[1]南京医科大学附属鼓楼临床医学院消化内科,江苏省南京市210008 [2]南京大学医学院附属鼓楼医院消化科,江苏省南京市210008

出　　处：《世界华人消化杂志》2010年第9期889-896,共8页World Chinese Journal of Digestology

基　　金：江苏省卫生厅医学重点人才基金资助项目;No.RC2007003~~

摘　　要：目的:探讨胃癌RUNX3、RASSF1A基因启动子甲基化在胃癌进展转移中的作用及意义.方法:RT-PCR和MSP检测62例胃癌标本及56例正常胃黏膜组织RUNX3、RASSF1A基因mRNA表达及甲基化状况,免疫组织化学检测VEGF在RUNX3、RASSF1A甲基化与非甲基化胃癌组织及20例正常组织中的表达,并分析RUNX3、RASSF1A甲基化与VEGF表达的关系.结果:胃癌组织RUNX3与RASSF1A表达较正常组织均明显降低(0.629±0.461vs0.893±0.543,0.653±0.476vs0.858±0.581,均P<0.05),且RUNX3与RASSF1A甲基化率均高于正常组织(69.4%vs26.8%,66.1%vs23.2%,均P<0.01).胃癌组织中RUNX3、RASSF1A甲基化组mRNA表达量较非甲基化组明显降低(0.545±0.299vs0.736±0.291,0.562±0.208vs0.674±0.185,均P<0.05).RASSF1A甲基化与肿瘤TNM分期及浸润深度相关,RUNX3甲基化与肿瘤淋巴结转移、血管侵犯及TNM分期相关(P<0.05).RUNX3甲基化组胃癌组织VEGF蛋白表达高于非甲基化组(86.0%vs57.9%),RUNX3甲基化与VEGF表达相关(P<0.05).结论:RUNX3、RASSF1A启动子高甲基化可能是导致其表达降低的原因,并与胃癌进展演变相关.RUNX3甲基化可能参与胃癌血管、淋巴管转移.AIM： To investigate the clinical significance of runt-related transcription factor 3 （RUNX3） and Ras association domain family 1A （RASSF1A） promoter methylation in human gastric cancer. METHODS： The mRNA expression and methylation of RUNX3, and RASSF1A in 62 gastric cancer specimens and 56 adjacent normal tissue specimens were detected by reverse transcription-polymerase chain reaction （RT-PCR） and methylation-specific PCR （MSP）, respectively. The expression of VEGF protein was measured by immunohistochemistry in methylation-positive and -negative cancer tissue specimens and 20 normal gastric tissue specimens. RESULTS： The mRNA expression levels of RUNX3 and RASSF1A in gastric cancer were lower than those in normal gastric tissue （0.629 ± 0.461 vs 0.893 ± 0.543 and 0.653 ± 0.476 vs 0.858 ± 0.581, respectively; both P 0.05）. The positive rates of RUNX3 and RASSF1A methylation were significantly higher in gastric cancer tissue specimens than in normal control ones （69.4% vs 26.8% and 66.1% vs 23.2%, respectively; both P 0.01）. The expression levels of RUNX3 and RASSF1A mRNAs were lower in methylation-positive cancer tissue specimens than in methylation-negative ones （P 0.05）. Neither RUNX3 nor RASSF1A promoter methylation were correlated with sex, age, tumor size, tumor differentiation degree, and Lauren classification. However, RASSF1A methylation was related with TNM stage and depth of infiltration, and RUNX3 methylation was associated with lymph node metastasis, vascular invasion and TNM stage. The positive rate of VEGF protein expression in RUNX3 methylation-positive gastric cancer specimens was significantly higher than that in RUNX3 methylation-negative ones （86.0% vs 57.9%, P 0.05）. CONCLUSION： Aberrant RUNX3 and RASSF1A promoter methylation may lead to down-regulation of the two genes in GC and is therefore involved in the progression of the disease. RUNX3 promoter methylation may participate in the vascular/lymphatic metastasis of GC.

关 键 词：胃肿瘤 甲基化 RUNX3 RASSF1A 血管内皮生长因子 

分 类 号：R735.2[医药卫生—肿瘤]