The identification of prostate cancer associated tumour antigens and biomarkers

Dede, A.Y., 2015. The identification of prostate cancer associated tumour antigens and biomarkers. PhD, Nottingham Trent University.

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Abstract

The widespread use of Prostate Specific Antigen (PSA) testing has resulted in the over detection and over treatment of potentially indolent disease due to the lack of specificity of PSA for prostate cancer (PCa). PROTEOMEX, a method of tumour associated antigen (TAA) identification, combines the separation of tumour proteins by conventional proteomic methods (2-DE and mass spectrometry) with serological screening using serum antibodies, to identify immunogenic proteins in cancer. This project aims to identify TAAs and/or biomarkers for PCa which on subsequent validation, can be utilised as an improved diagnostic screening test. In pilot studies, SDS PAGE, 2-DE and OFFGEL electrophoresis were performed to identify immunogenic urine TAAs using PCa and healthy control sera. Proteins within the serum-reactive spots were either identified by Liquid Chromatography coupled to Matrix-Assisted Laser Desorption/Ionisation Time-of-Flight mass spectrometry (MALDI-TOF MS) or Electrospray Ionisation mass spectrometry (ESI MS). Among the urinary proteins separated by SDS PAGE, 2-DE and OFFGEL respectively, exclusive autoreactivity was identified in PCa sera to serum albumin and existing PCa biomarkers - human prostatic acid phosphatase & zinc-alpha-2 glycoprotein. Differential autoantibody responses were also identified to various TAAs in the PC-3 and DU-145 PCa cell lines using PCa and healthy sera. The presence of a differential TAA and autoantibody PCa serum response to one of the proteins identified by MALDI-TOF, alpha enolase, was further verified in a subset of PCa samples using immunohistochemistry, Western blotting and ELISA. In a larger sample cohort, the cytoplasmic and nuclear alpha enolase expression in a PCa TMA was assessed, where statistical significance was observed between benign controls and PCa (p=0.000003 and p=0.003 respectively), although protein expression did not correlate with any important clinico-pathological variables. Alpha enolase autoantibody expression was statistically significant between PCa and healthy controls (p=0.0038), where its expression correlated with D’Amico risk classification, indicating that alpha enolase may serve as a potential indicator of biochemical recurrence in PCa. PROTEOMEX represents a valuable approach for the identification of tumour biomarkers which may have diagnostic and/or prognostic value in PCa. Further work should identifiy more TAAs and autoantibodies associated with PCa, alongside a validation of the diagnostic utility of the identified biomarkers from this study.

Item Type:	Thesis
Creators:	Dede, A.Y.
Date:	June 2015
Rights:	This work is the intellectual property of the author, and may also be owned by the research sponsor(s) and/or Nottingham Trent University. You may copy up to 5% of this work for private study, or personal, non-commercial research. Any re-use of the information contained within this document should be fully referenced, quoting the author, title, university, degree level and pagination. Queries or requests for any other use, or if a more substantial copy is required, should be directed to the owner(s) of the Intellectual Property Rights.
Divisions:	Schools > School of Science and Technology
Record created by:	Linda Sullivan
Date Added:	03 Jun 2016 15:36
Last Modified:	03 Jun 2016 15:36
URI:	https://irep.ntu.ac.uk/id/eprint/27929

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