Hepatocellular Carcinoma Patients Highly and Specifically Expressing XAGE-1 Exhibit Prolonged Survival

XAGE-1 is classified into the group of a new family of cancer-testis antigens (CTA) and has the four transcript variants of XAGE-1a, XAGE-1b, XAGE-1c and XAGE-1d. Immunohistochemistry was used to investigate the expression of XAGE-1 transcript variants in Chinese patients with hepatocellular carcinoma (HCC). Reverse transcription-polymerase chain reaction (RT-PCR) and real-time RT-PCR were used to analyze XAGE-1 gene expression, and XAGE-1 protein expression was examined by immunohistochemistry. Furthermore, the clinical correlation of XAGE-1 expression was analyzed. The expression of the XAGE-1 mRNA was investigated in the tissues of 96 HCC patients and all XAGE-1 isoforms were detected in these tissues. Three types of XAGE-1 transcript variants (XAGE-1b, XAGE-1c and XAGE-1d) showed high specific and frequent expression in HCC tissues, with the positive expression rate of XAGE-1b, XAGE-1c and XAGE-1d being 41.7% (40/96), 15.6% (15/96) and 26.0% (25/96), respectively. XAGE-1b was the dominant type, but none of the three were detected in adjacent non-HCC tissues. Only 2 cases of XAGE-1a mRNA expression were observed. Moreover, XAGE-1 protein was detected in 39 of 96 HCC patients, but none in the adjacent non-cancerous tissue and normal liver tissue. No relationship was found between the expression of XAGE-1 and clinical parameters, such as age, gender, tumor size, TNM staging, serum AFP level and infection with hepatitis virus. Patients with XAGE-1b-positive transcript variant exhibited shorter 2-year survival times. The high frequency and specificity of XAGE-1, particularly XAGE-1b, in HCC indicates that their products may predict the prognosis of HCC patients and be novel targets for antigen-specific immunotherapy to HCC.