CT antigens are potential targets for cancer immunotherapy because of their restricted expression in immune-privileged germ cells and various malignancies. Current application of CT-based immunotherapy has been focused on CT expression-rich tumors such as melanoma and lung cancers. In this study, we surveyed CT expression to a larger extent using the TCGA datasets for ten common cancer types. We show that, in addition to cancer-specific CT expression, CT expression is also enriched within cancer molecular subtypes. For example, HORMAD1, CXorf61, ACTL8 and PRAME are highly enriched in the basal subtype of breast cancer; MAGE and CSAG genes are most frequently activated in the magnoid subtype of lung adenocarcinoma; and PRAME is highly upregulated in the ccB subtype of clear cell renal carcinoma. Correlation between gene expression and methylation suggests that CT expression is controlled through various mechanisms: some CTs are more subject to epigenetic regulation while others may be controlled primarily by tissue-specific and subtype-specific transcription factors. Our results also suggest that although for some CTs expression is associated with patient outcome, fewer are independent prognostic markers. Thus, CTs bearing a shared expression pattern are a group of heterogeneous molecules with distinct activation modes and functional properties in different cancers and cancer subtypes. These data suggest a cancer subtype-orientated application of CT antigen as biomarkers and immunotherapeutic targets.
- Received July 5, 2013.
- Revision received November 13, 2013.
- Accepted November 14, 2013.
- Copyright © 2013, American Association for Cancer Research.