Identification of Novel Human Cancer-Specific Antigens

Rasha Ali Hussain Al-Khafaji
  • Radiology Department, Regional Hospital Midt, Viborg, Denmark
  • Keywords:
  • Cancer Testis Antigens, Cancer Vaccination, Immunotherapy, Meiosis, Infertility
  • Abstract:
  • Cancer imposes continuous challenges on global health, and the trend of its incidence will make it the leading cause of mortality in the twenty-first century (Robert, Vries & Hans 2010). Therefore, identifying novel-cancer antigens that can be used as biomarkers and targets for therapeutics has been a priority to minimize cancer morbidity and mortality rates (Grizzi et al. 2007).
  • Cancer testis antigens genes’ (CTAs) characteristics of immune privilege restricted expression, aberrant expression in unrelated histological malignancies, and immunogenicity have made them a valuable family to be exploited for cancer research and clinical therapeutics (Joseph-Pietras et al. 2010; Shigematsu et al. 2010).
  • Germ cell characteristics, such as global hypomethylation, telomerase activity, CTA expression, and the presence of several meiosis stage-specific proteins, are common features in cancer. Therefore, many sperm-specific proteins may contain novel-cancer testis antigens (Silina et al. 2011; Gjerstorff et al. 2010; Gjerstorff, Burns & Ditzel 2010).
  • Through whole-genome profiling of male germline expression in mice, rats, and humans, several loci have shown a conserved sequence in meiotic and post-meiotic profiles. Though hybridization of the mice testis mRNA to human testis tissue, a microarray study revealed a positive signal of 81% from the clones (Sha et al. 2002). These are likely essential for sexual production, and several have detectable expression profiles in cancers. Therefore, as previously states, gametogenesis and carcinogenesis may share a similar molecular mechanism (Chalmel, Lardenois & Primig 2007)
  • Given this, our research group has designed an in silico pipeline analysis that has identified a high number of candidate cancer-specific markers that could be promising in the oncology field. Using this approach, C4orf35, C13orf28, C18orf54, C20orf195, C22orf33, PPP4R4, SPACA1, and TMCO2 have been filtered.
  • According to Hofmanna et al. (2008), gene expression in a CTA is restricted to the testis and cancer; furthermore, Mobasheri et al. (2007) found that a good CTA candidate should only be expressed in testis and cancer cell lines. Therefore, we analysed an expression profile of these genes in a panel of normal tissue samples by semi-quantitative RT-PCR using tailored primers for each candidate; b-actin was used as an unchanged and fixed endogenous gene reference. Only upon testis restricted gene expression will a gene be validated for screening in our designed panel of cancer samples
  • Our research is small in size, of an exploratory nature, and was not designed to quantify expression; rather, it is designed as a preliminary validation of several genes that were categorised for meiosis and cancer expression. However, our results should not be over-looked. In the given set of the XV. experiment, the author has managed to identify C22orf33 and SPACA1 as potential candidates. In spite of having additional expression in the thymus, C18orf54 is also a good candidate. As will be demonstrated, all remaining genes, with the exception of TMCO2, could have potential use in the field of oncology field through the cautious interpretation of currently available data. Our study is not large enough to answer many questions related to these genes, provide further information on a putative function of these expressions, or validate the available data. As such, further experiments on a broader scale are warranted.
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Identification of Novel Human Cancer-Specific Antigens
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