Identifying potential new stem cell biomarkers for prostate cancer

Abstract

Few biomarkers have been identified for prostate cancer diagnosis/prognosis and there are clinical difficulties in distinguishing between relapsing and non-relapsing tumours. Therefore, identifying new biomarkers for prostate cancer has become a priority. Recently, potential stem cells found within a tumour have received a lot of attention and it is thought that these cells may have a role in cancer initiation, progression and drug resistance. The major goal of this study was to focus on proteins linked to stem cells, cellular differentiation and/or tumour formation and progression and establish if they are differentially expressed between normal and malignant prostate tissues and/or between samples with different clinical features, including relapsing vs non-relapsing tumours.
Eight potential biomarkers were identified using literature searching. These were β-catenin, NDRG1, ABCG2, ALDH1A1, RS1, Sox7, Sall4 and Zscan4. Their expression was evaluated by immunohistochemistry using 39 prostate tissue samples from a Bath cohort and the staining was then repeated using a much larger tissue microarray cohort that consisted of 96 cases. The data from both cohorts was then tested for association with different clinical features. Finally, the expression of three of the potential biomarkers, Sox7, Sall4 and Zscan4 was further validated by staining tissues from both cohorts with either a second independent antibody and /or for the biomarkers’ mRNA using RNAscope®.
β-catenin, Sox7, ABCG2, membranous and cytoplasmic NDRG1 staining was found to be reduced in prostate cancer samples, whereas, Zscan4, nuclear NDRG1 and Sall4 staining was increased. There was a negative association between β-catenin, Sox7, ABCG2 and Sall4 staining and increasing Gleason grade, whereas, nuclear NDRG1 staining was positively associated with Gleason grade. There was also a negative association between Sox7, ABCG2 and stromal ALDH1A1 staining and biochemical relapse. In contrast, there was no significant association between RS1 staining and prostate cancer clinical features. Therefore, this data identified seven proteins that may play a role in prostate tumour formation and/or aggressiveness and three that may be implicated in PCa relapse. These candidates warrant further investigation to understand their functions and establish if they could represent potential diagnostic/prognostic biomarkers for prostate cancer.

Date of Award	19 Jun 2019
Original language	English
Awarding Institution	University of Bath
Sponsors	Ministry of Higher Education and Scientific Research - Iraq & Thi Qar University
Supervisor	Andrew Chalmers (Supervisor), Paul Whitley (Supervisor), Mark Beresford, (Advisor), Rebecca Bowen (Advisor) & John Mitchard (Advisor)