Cancer is a highly complex disease that evolved in response to a wide range of biological and molecular changes that impact disease behaviour, treatment efficacy and clinical outcomes. Studying this diversity in human tumours is essential for gaining insights that will ultimately improve the survival rates of cancer patients. Cancer stem-like cells (CSCs) are believed to be responsible for invasive and metastatic features in tumours and can contribute to chemotherapy resistance and subsequent tumour relapses. There is an increasing need to identify the molecular mechanisms involved in tumour cells, particularly in CSCs. Cancer testis antigens (CTAs) are a subclass of germline proteins normally produced in immune-privileged sites, such as the testis, ovary and placenta of somatic tissues, and the presence of these antigens is increased in a variety of cancers. These characteristics make CTAs highly important immunotherapeutic targets, since they do not harness the immune response in the testes but encode immunogenic proteins that can induce a specific response in cancerous tissues. CTA genes are potentially very importance in clinical applications, including cancer diagnosis, vaccination and immunotherapy. This current study focused on the investigation of two CTAs, TDRD12 and LKAAEAR1, that may have an enhanced presence in cancer and the potential to be immunogenic. TDRD12 is linked to stemness features and enables the proliferation of germ line tumour cells. It appears to act as a possible transcriptional regulator for germline factors that are essential to cell cycle proliferation, germ cell maintenance and stem marker expression. TDRD12 may have the potential to drive oncogenesis and CSC targets. LKAAEAR1 was validated as a CTA at the protein level, showing its production was restricted to germ cells and the central nervous system from normal tissues and showed aberrant production in a wide range of tumours. This protein has been shown to be produced in germ cells undergoing spermatogenesis with strong nuclei staining, suggesting its potential role in this process. LKAAEAR1 potentially acts as a regulator for transposable elements, thereby increasing its contributions to cancer development. This study demonstrated that LKAAEAR1 could potentially be used as a cancer biomarker and therapeutic target.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:767449 |
| Date | January 2019 |
| Creators | Alsulami, Mishal |
| Contributors | Mcfarlane, Ramsay |
| Publisher | Bangor University |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | https://research.bangor.ac.uk/portal/en/theses/characterisation-of-human-tdrd12-and-lkaaear1-as-potential-oncogenic-cancer-testis-antigen-genes-with-clinical-potential(2e569d4d-8a11-4bdf-9245-21f019a16ccb).html |
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