Expression of Cancer Testis (CT) genes is normally restricted to testis and placenta, but these genes are also aberrantly activated in tumours of distinct origins, with PRAME, MAGE, GAGE and ESO/LAGE family members encoding cancer testis antigens (CTAs) that stimulate tumorigenesis and elicit immune response. This makes CT genes/CTAs unique biomarkers and potential anticancer therapeutic targets. In this work, we screened the gene expression profiles of a panel of normal tissues and identified 1345 Testis-biased genes, with the aim of correlating subgroups with tumour expression profiles and identify potential oncogenic functional clusters. We also characterised various functional aspects of a benchmark CT gene, TEX19, namely transcript levels during phases of embryogenesis and spermatogenesis, aiming to establish parallelism with its transcriptional and posttranscriptional regulation in cancer.
The findings of this study showed that Testis-biased genes are mostly downregulated in testicular tumours, which comprise seminoma, embryonal carcinoma, yolk sac and teratoma as the major subtypes, while in other solid malignancies, these genes are mostly upregulated when differentially expressed. Since more than 90% of testicular tumours have origin in germ cells, this could suggest impairment of germ-like features either as a cause or consequence of testicular tumours, while the CT gene activation in other solid tumours may not be necessarily linked to an attempt to enter a testis programme.
Novel functional aspects involving TEX19 were unravelled, with this protein co-localising with UBR2 in distinct nuclear foci in some cancer cell lines, in addition to the inter-regulation that was previously observed between these two proteins. TEX19 could be involved in DNA damage repair in cancer since the levels of RAD51 and γH2AX were seen to be altered upon TEX19 depletion in cancer cells. In addition, TEX19 was shown to have a reciprocal regulatory relationship with L1 elements.
Finally, monoclonal antibodies targeting TEX19 were developed, opening future possibilities of developing assays to detect TEX19 in cancer diagnosis, or to target this protein in anticancer therapy.
Keywords: Biomarkers, Cancer Testis (CT), Embryogenesis, Germline, Monoclonal antibody, Placenta, Spermatogenesis, Testis, TEX19, Transposable elements.