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The poor prognosis of liver cancer demands the development of new diagnostic markers and therapeutic strategies. Cancer/testis (CT) antigens are expressed in the testis and cancerous tissues, but not in adult somatic cells. Given their tumor-specific expression, CT antigens are potential molecular markers for tumor diagnosis and targets for cancer immunotherapy. To identify novel CT antigens for liver cancer, we examined mRNA expression of hitherto unknown CT antigen candidates, tudor domain-containing protein (TDRD) 1, 4 and 5 in three types of liver cancer; hepatocellular carcinoma (HCC, n = 28), cholangiocarcinoma (CC, n = 5) and combined HCC-CC (n = 8), with matched non-tumorous liver tissues. The TDRD1, 4 and 5 are known as being specifically expressed in the testis. TDRD1 and 5 are essential for male germ cell development. On RT-PCR analysis, TDRD1 mRNA was expressed in both HCCs and non-tumorous liver tissues, and TDRD5 mRNA was expressed in normal colonic and gastric mucosal tissues. Thus, TDRD1 and TDRD5 are not candidates for CT antigens. TDRD4 mRNA was expressed in the testis but not in other normal tissues, including colonic mucosa, gastric mucosa, and liver tissues. TDRD4 mRNA was expressed in 7 of the 41 liver cancers: 4 HCCs, 1 CC and 2 combined HCC-CCs. The TDRD4 mRNA expression was not significantly associated with patient age, tumor size, pathologic stages, hepatitis B virus infection, or CD133 expression. In conclusion, TDRD4 mRNA is expressed in a subset of liver cancers, and TDRD4 is a candidate CT antigen for liver cancer.

Tudor Domain-Containing Protein 4 as a Potential Cancer/Testis Antigen in Liver Cancer