黑色素瘤抗原-1基因在肝细胞癌中的表达  

Expression of MAGE-1 gene in hepatocellular carcinoma

作　　者：蔡胜利[1] 陈红松[2] 王瑜[3] 赵海涛[4] 彭吉润[1] 庞学文[3] 龚顺友[3] 朱继业[1] 丛旭[2] 王宇[2] 芮静安[4] 冷希圣[1] 杜如昱[1] 陈慰峰[3] 

机构地区：[1]北京医科大学人民医院外科,100044 [2]北京医科大学人民医院肝病研究所 [3]北京医科大学基础医学院免疫学系 [4]邮电总医院肝癌研究所

出　　处：《中华医学杂志》1999年第9期668-672,共5页National Medical Journal of China

基　　金：国家自然科学基金!3 983 0 42 0 ;北京医科大学和澳大利亚合作项目

摘　　要：目的　检测黑色素瘤抗原 1(MAGE 1)mRNA在肝细胞癌 (HCC)中的表达 ,为用MAGE 1基因编码蛋白作为疫苗对HCC患者进行免疫治疗提供依据。方法　用逆转录 聚合酶链反应 (RT PCR)方法对 4 5例HCC患者癌组织和相应癌旁肝组织以及 16例肝硬化组织和 12例正常肝组织的MAGE 1mRNA表达情况进行研究 ,对 6例RT PCR扩增产物中的目的基因片段进行DNA序列测定 ,并以测序证实为MAGE 1基因的cDNA片段为模板合成 [α32 P]标记的探针 ,进行Southernblot分析。同时用ELISA方法对其中 4 3例HCC患者进行人类白细胞抗原 (HLA)class1 A及B位点分型。结果　 4 5例HCC患者中 ,3 2例表达MAGE 1mRNA ,而相应癌旁组织及非HCC患者肝组织均不表达 ;DNA测序 ,6例PCR产物中的目的基因片段均证明为MAGE 1cDNA序列 ,其中 3例均有 3个相同位置碱基的点突变 ,导致 2个氨基酸残基改变 ;5例电泳阳性癌组织的RT PCR产物Southernblot结果也为阳性 ,而癌旁组织均为阴性 ;HCC患者中常见HLA类型为A2 ( 5 3 5 % ) ,A11( 2 5 6% ) ,A2 4( 2 0 9% ) ,A33( 2 0 9% ) ,B13( 2 8 3 % ) ,B35( 2 3 2 % ) ;MAGE 1的表达与肿瘤直径、α FP水平等临床指标无相关关系。结论　MAGE 1在肝细胞癌中呈高比例表达 。Objective To investigate the expression of MAGE 1 mRNA in human hepatocellular carcinoma (HCC) and to discuss the possibility of using MAGE 1 antigens as a new peptide vaccine for immunotherapy for HCC Methods The expression of MAGE 1 mRNA in HCC tissue and the adjacent non HCC liver tissue was detected using RT PCR in 45 samples of HCC, 16 samples of cirrhosis and 12 samples of normal liver tissue. The 6 samples of MAGE 1 mRNA positive PCR products were DNA sequenced The sequenced fragments of MAGE 1 cDNA were used as template to which a [α 32 P] labeled probe was synthesized and employed for Southern blot analysis HLA class I A and I B typing of 43 HCC patients were assayed by ELISA test Results Of the 45 HCC samples, 32 expressed MAGE 1 mRNA None of the HCC adjacent tissue or liver tissue from cirrhosis or normal liver samples expressed MAGE 1 mRNA. The DNA sequence confirmed that the target gene fragment in all the 6 samples of PCR products was MAGE 1 cDNA Point mutation occurred in 3 samples resulting in alternation of amino acid residues in 2 positions Southern blot analysis showed that MAGE 1 was also detectable in HCC tissue which was MAGE 1 positive in RT PCR assay, but not detectable in non HCC liver tissue In HCC patients, the predominant types of HLA were A 2 (53 5%), A 11 (25 6%), A 24 (20 9%), A 33 (20 9%), B 13 (28 3%) and B 35 (23 2%) MAGE 1 mRNA expression in HCC showed no correlation with the level of α FP in blood and the diameter of tumor Conclusions MAGE 1 mRNA is expressed at a high percentage of HCC samples This tumor rejection antigen may have potential to be used as a new peptide vaccine for immunotherapy for HCC There are point mutations of MAGE 1 gene sequence in some Chinese HCC patients

关 键 词：黑色素瘤 肝细胞癌 抗原1-基因 基因表达 

分 类 号：R735.7[医药卫生—肿瘤]