Identification of Novel Human Cancer-Testis-Antigen Genes in Cancers

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  • Mikhlid Almutairi

    Research areas

  • PhD, School of Biological Sciences

Abstract

Cancer is a large group of diseases that can result in substantially increased mortality. This increased mortality occurs not only due to the limited effectiveness of the available treatments, but also because the diagnosis usually occurs late in the tumour development.
Therefore , the identification of new cancer-specific biomarkers is extremely important in order to improve patient diagnosis at an early stage. Humans possess a class of genes that are normally expressed in the testes of adult males, and are also characteristic of several types of cancer cells. These genes are known as cancer-testis (CT) antigen genes and they might be
helpful for both diagnosis and immunotherapy drug targeting. For this reason, identifying new CTA genes has significant clinical importance. Meiosis
is restricted to germ cells and a number of meiotic proteins have previously been identified as CT antigens; consequently, we postulated that meiosis-
specific genes may provide a good source for identifying potential
novel CTA genes.
Potential meiotic genes were identified from a bioinformatics analysis. The specificity of these meiosis genes was validated in several types of normal human tissues. Genes that were found to display testis-restricted/selective or testis-CNS-restricted/selective expression profiles in the normal tissues were further screened in a wide range of cancer tissues and cancer cell lines. Out of the 32 genes screened by RT-PCR in the present study, the results identified 11 genes as novel CT genes. From the 11 candidate CT
genes, STRA8 and C20orf201 were further functionally characterised in cancer cells.
The STRA8 and C20orf201 genes are considered to be good CT candidate genes since they are expressed in different types of cancer.Further analysed
of STRA8 and C20orf201 by developing overexpression cell lines and this
work indicates they have CTA potential. Expression of STRA8 subcloned into Flp-In T-REx-293 cells did not reveal obvious functional activity.
C20orf201 gene was validated in this study at the protein levels in different normal and cancer tissue and cell lines. C20orf201 was found in
the normal human testes and central nervous tissues. However, C20orf201 was also found to be present in a range of cancer cells suggesting it could be a CTA; biochemical evidence is also presented to indicate it might have
functional activity as it appears to be modified in cancer-specific fashion.

Details

Original languageEnglish
Awarding Institution
Supervisors/Advisors
Thesis sponsors
  • King Saud University
Award date8 Sept 2014