CTexploreR: taking on the challenge of Cancer-Testis genes

Author(s): Julie Devis,Axelle Loriot,Charles De Smet,Laurent Gatto

Affiliation(s): UCLouvain

Social media: https://twitter.com/JulieDevis

Cancer-Testis (CT) genes are tissue-specific genes whose expression is limited to the germline. They are normally repressed in somatic tissues, but can be aberrantly activated in tumors. For many CT genes, tumoral activation is enabled by loss of promoter DNA methylation. CT genes are of great interest. First, they have clinical potential as cancer-specific antigens, and can thus be used as target for cancer immunotherapy and as cancer biomarkers. Second, they are also a good model to study DNA demethylation in cancer, which is still poorly understood. The definition of CT genes differs vastly according to the literature source. Some databases already exist (Almeida et al., 2009; Jamin et al., 2021; Wang et al., 2016) but they are neither up-to-date nor well annotated, and thus difficult to use. There is therefore a need for a reliable and reproducible resource when studying CT genes. We therefor created CTexploreR, a package that rigorously defines and explores CT genes. Our main objective was to propose a reliable and well-defined list of CT genes based on publicly available RNAseq databases. We also determined their precise transcription start site in order to be able to realise an accurate promoter methylation analysis. Our list contains 307 CT genes that were carefully classified as regulated by DNA methylation or not. We also developed functions to visualise CT genes expression and promoter DNA methylation in normal and tumoral tissues. We also performed a thorough comparison of CTexploreR with the available resources mentioned above. It allowed us to clearly establish and characterise the difference between CT lists and clarify the origins of the inconsistencies. These analyses demonstrate that CTexploreR is a clear, curated and rigorously established up-to-date reference. Our package can thus be used as the starting point for further investigations. - Almeida, L. G., Sakabe, N. J., deOliveira, A. R., Silva, M. C. C., Mundstein, A. S., Cohen, T., Chen, Y.-T., Chua, R., Gurung, S., Gnjatic, S., Jungbluth, A. A., Caballero, O. L., Bairoch, A., Kiesler, E., White, S. L., Simpson, A. J. G., Old, L. J., Camargo, A. A., & Vasconcelos, A. T. R. (2009). CTdatabase: a knowledge-base of high-throughput and curated data on cancer-testis antigens. Nucleic Acids Research, 37(Database issue), D816-9. - Jamin, S. P., Hikmet, F., Mathieu, R., Jégou, B., Lindskog, C., Chalmel, F., & Primig, M. (2021). Combined RNA/tissue profiling identifies novel Cancer/testis genes. Molecular Oncology, 15(11), 3003–3023. - Wang, C., Gu, Y., Zhang, K., Xie, K., Zhu, M., Dai, N., Jiang, Y., Guo, X., Liu, M., Dai, J., Wu, L., Jin, G., Ma, H., Jiang, T., Yin, R., Xia, Y., Liu, L., Wang, S., Shen, B., … Hu, Z. (2016). Systematic identification of genes with a cancer-testis expression pattern in 19 cancer types. Nature Communications, 7, 10499.