Zhao Li, Mou Dong-Cheng, Leng Xi-Sheng, Peng Ji-Run, Wang Wan-Xiang, Huang Lei, Li Shu, Zhu Ji-Ye
Center of Hepatobiliary Surgery, People's Hospital, Peking University, 11 XiZhimen Nandajie, West District, Beijing 100044, China.
World J Gastroenterol. 2004 Jul 15;10(14):2034-8. doi: 10.3748/wjg.v10.i14.2034.
To investigate the expression of cancer-testis (CT) antigens MAGE-1, SSX-1,CTp11 and HCA587 genes in hepatocellular carcinoma (HCC) and the possibility of applying these antigens as targets for specific immunotherapy for HCC.
Expression levels of MAGE-1, SSX-1, CTp11 and HCA587 mRNA were detected with reverse transcription polymerase chain reaction (RT-PCR) in HCC tissues and corresponding adjacent non-cancerous tissues from 105 HCC patients, 40 samples of cirrhosis and normal liver tissues. Genes of five samples with positive PCR results were sequenced.
Of 105 HCC tissues, MAGE1, SSX-1,CTp11 and HCA587 mRNA expressions were detectable in 75.2%(79/105), 72.4%(76/105), 62.9%(66/105) and 56.2%(59/105) of HCC samples, respectively. About 93.3%(98/105), 72.4%(76/105), 48.6%(51/105) and 37.1%(39/105) of HCC tissues positively expressed at least one, two, three, and four members of CT antigens, respectively. Conversely, only SSX-1 could be detectable in 2.9%(3/105) of the corresponding adjacent non-HCC tissues in which no metastatic lesion was found. Of the latter 3 patients, biopsy samples far from tumor were obtained in 2 patients and RT-PCR indicated no expression of SSX-1 mRNA in these two samples. In addition, none of 40 samples of cirrhotic and normal liver tissues expressed CT antigen gene mRNA. DNA sequences confirmed that the RT-PCR products were true target cDNA. No relationship was found between expression of CT antigens and clinico pathological indicators such as age, gender, tumor size, degree of tumor differentiation, serum alpha-fetoprotein level and infection of hepatitis B virus or hepatitis C virus (P>0.05).
CT antigens genes (MAGE-1, SSX-1, CTp11 and HCA587) are expressed with high percentage and specificity in HCC and their products are promising targets for antigen-specific immunotherapy of HCC. High frequent co-expression of multiple members of CT antigens in HCC provides possibility of polyvalent vaccinations for HCC.
研究癌-睾丸(CT)抗原MAGE-1、SSX-1、CTp11和HCA587基因在肝细胞癌(HCC)中的表达情况,以及将这些抗原作为HCC特异性免疫治疗靶点的可能性。
采用逆转录聚合酶链反应(RT-PCR)检测105例HCC患者的HCC组织及相应癌旁非癌组织、40例肝硬化组织和正常肝组织中MAGE-1、SSX-1、CTp11和HCA587 mRNA的表达水平。对5例PCR结果阳性的样本进行基因测序。
在105例HCC组织中,MAGE1、SSX-1、CTp11和HCA587 mRNA的表达率分别为75.2%(79/105)、72.4%(76/105)、62.9%(66/105)和56.2%(59/105)。分别约有93.3%(98/105)、72.4%(76/105)、48.6%(51/105)和37.1%(39/105)的HCC组织至少阳性表达一种、两种、三种和四种CT抗原成员。相反,在未发现转移灶的相应癌旁非HCC组织中,仅2.9%(3/105)可检测到SSX-1。在这3例患者中,2例获取了远离肿瘤的活检样本,RT-PCR显示这两个样本中无SSX-1 mRNA表达。此外,40例肝硬化组织和正常肝组织样本均未表达CT抗原基因mRNA。DNA序列证实RT-PCR产物为真正的靶标cDNA。未发现CT抗原表达与年龄、性别、肿瘤大小、肿瘤分化程度、血清甲胎蛋白水平及乙型肝炎病毒或丙型肝炎病毒感染等临床病理指标之间存在相关性(P>0.05)。
CT抗原基因(MAGE-1、SSX-1、CTp11和HCA587)在HCC中高比例且特异性表达,其产物有望成为HCC抗原特异性免疫治疗的靶点。HCC中多种CT抗原成员的高频率共表达为HCC的多价疫苗接种提供了可能性。