Prostate cancer-associated protein biomarkers in African heritage populations

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Goodall, P., 2021. Prostate cancer-associated protein biomarkers in African heritage populations. MPhil, Nottingham Trent University.

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Abstract

Background: African Heritage (AH) men have a higher overall incidence, earlier age of onset, more clinically advanced and aggressive disease, higher incidence of metastases and mortality from prostate cancer (CaP) compared to Caucasian men. Biological and genetic factors relating to tumour biological pathways are thought to account for this disparity. Pathways associated with apoptosis and proliferation, cell adhesion and epithelial mesenchymal-transition (EMT), inflammation and host immune response
have all been implicated.

Aims and Objectives: We aimed to develop a panel of biomarkers related to these pathways likely to account for the disparity of aggressive disease between AH and Caucasian men with CaP. Specifically we aimed to identify potential candidate biomarkers that could potentially be used to predict clinical outcomes in these ethnic groups, review if they displayed differential expression and to confirm or negate relevant important biological pathways for possible therapeutic targeting.

Methods: A panel of candidate biomarkers was selected from an extensive literature review of biological tumour pathways in AH men with prostate cancer and a bioinformatic approach using an artificial neural network (ANN) analysis to identify biomarkers conferring increased risk of metastasis in AH men. Immunohistochemical analysis was performed on a Caucasian predominant historical tissue microarray (TMA) constructed from transurethral resection of prostate (TURP) and transrectal ultrasound guided (TRUS) prostate biopsy CaP samples. A new AH TMA was produced from radical prostatectomy and TURP samples. Univariate and multivariate analysis was performed to establish the association of protein biomarker expression with various clinical prognostic endpoints, specifically time to disease specific death and metastasis development.

Results: We demonstrated the utility of several biomarkers, Lambda FLC, TGF-β EPB41L4A and PD-L1, in predicting disease specific survival, time to metastasis development and castrate resistance. In particular increased protein expression of Immunoglobulin Free light chain (FLC) lambda FLC, which is a completely novel biomarker in CaP, was statistically significant in predicting disease specific death and time to metastases. Greater expression was seen in AH men.

Conclusions: We have identified a completely novel biomarker, Lambda FLC, in CaP with the prognostic ability to predict disease specific death and development of metastases with increased protein expression seen in AH men. Our study supports the hypothesis and findings from previous studies that suggest the regulation of inflammation and modulation of the immune system and resultant change in extracellular matrix (ECM), of the tumour microenvironment, appears to be an important biological process and might account for the aggressive nature of CaP in AH men.

Item Type:	Thesis
Creators:	Goodall, P.
Date:	March 2021
Rights:	This work is the intellectual property of the author. 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 in the owner of the Intellectual Property Rights.
Divisions:	Schools > School of Science and Technology
Record created by:	Linda Sullivan
Date Added:	08 Jul 2021 09:19
Last Modified:	08 Jul 2021 09:33
URI:	https://irep.ntu.ac.uk/id/eprint/43374