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AIM: 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.METHODS: Expression levels of MAGE-1, SSX-1, CTp11 and HCA587mRNA 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.RESULTS: Of 105 HCC tissues, MAGE1, SSX-1 ,CTp11 and HCA587mRNA expressions were detectable in 75.2%(79/105),72.4%(76/105), 62.9%(66/105) and 56.2%(59/105) of HCCsamples, 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 tumorwere 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 α-fetoprotein level and infection of hepatitis B virus or hepatitis C virus (P＞0.05).CONCLUSION: 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.