PROMOTER METHYLATION REGULATES MAGE-A3 EXPRESSION IN HEPATOCELLULAR CARCINOMA

Abstract

Hepatocellular carcinoma (HCC) represents one of the most common causes of cancer-related death worldwide, with few available treatment options. Cancer-testis antigens (CTAs), notably from the MAGE gene family, have opened new possibilities for improving immunotherapy in HCC due to their tumor-specific expression and high immunogenicity. However, the mechanisms regulating MAGE gene expression are largely unknown. This study explored mechanisms controlling the expression of MAGE-A3 and MAGE-C2. We utilized HCC organoid cultures derived from patient HCC tissues known to represent cancer epigenetic status more accurately than cell lines to study the MAGE gene family expression patterns and promoter methylation patterns. Our findings reveal that MAGE-A3 expression is correlated with hypomethylation of its promoter region, whereas MAGE-C2 expression does not show such a correlation, suggesting other epigenetic mechanisms may regulate it. These findings suggest possibilities for targeting DNA methylation to control MAGE-A3 expression in HCC. This study supports the exploration of CTAs in cancer immunotherapy and underscores the complexity of MAGE gene regulation in HCC.