Browsing by Subject "Prostate Cancer"

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    Open Access
    Optimizing PSMA scintigraphy for resource limited settings – a retrospective comparative study
    (2025) Kolade, Olumayowa Uwadiale; More, Stuart; Holness, Jennifer; Brink, Anita; Ayeni, Akinwale
    Methods: The scans of 95 patients with histologically proven PCa who underwent PS with full-body planar and multi-FOV SPECT/CT were reviewed. The detection rates for uptake in the prostate gland/bed and in metastases were compared on planar, SPECT, and SPECT/CT. The agreement between modalities was calculated for the detection of metastases and for staging. The impact of imaging a limited FOV was determined
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    Open Access
    The contribution of population-specific PRIM2 variants to prostate cancer
    (University of Cape Town, 2026) Foret, Chiara; Wium, Martha; zerbini luiz
    Prostate cancer is a global health concern, with rates of incidence and mortality on the incline in all men. However, ethnic disparities in disease onset and outcome disproportionately affect African-descent men with prostate cancer, who harbour higher burden and aggressiveness of disease. Yet, the molecular mechanisms underlying this phenomenon have yet to be elucidated. Using previously published whole-genomics sequencing data from 12 South African prostate cancer patients (the SAPCa cohort), we observed a high level of somatic alterations in DNA primase subunit 2 (PRIM2). As the regulator of DNA primase, PRIM2 plays an important role in the preservation of genome integrity. Through comparative analysis with a Eurocentric genomics database (the TCGA), we noted that PRIM2 variants were more frequent in our African-descent cohort. After pathogenicity prediction by AlphaMissense, we selected PRIM2 missense variants that may hold clinically relevance to our cohort for further characterisation: p.Arg289His for its increased frequency within the SAPCa, and p.Arg302Cys for its novelty and high pathogenicity score. Since PRIM2 binds a [4Fe4S]2+/3+ cluster that regulates its DNA-binding activity, we employed Multi-Conformer Continuum Electrostatics to simulate its electrochemical midpoint potential within PRIM2 variant protein structures in situ. We postulate that p.Arg289His may enhance the activity of PRIM2 due to increased occupation of its [4Fe4S]2+/3+ cluster in the active Fe3+ state. Additionally, in vitro gain-of-function assays found that p.Arg289His promoted cellular migration and proliferation in both normal and cancerous prostate cells. Furthermore, we observed that p.Arg302Cys may promote the progression of EMT in normal prostate cells. To elucidate the underling mechanisms of the phenotypes observed in vitro, RNA sequencing was performed on the prostate cancer cells expressing the PRIM2 variants. Ingenuity Pathway analysis of the generated differential gene expression profiles revealed that the S100 family of proteins (broadly implicated in numerous cancers) was commonly activated in both PRIM2 variants. We also observed that p.Arg289His enriched pathways involved in immunosuppression and biosynthesis of metabolites which may (facilitate a favourable tumour microenvironment), while p.Arg302Cys enriched receptor kinase signalling and pathways associated with rare complications of metastatic prostate cancer. Therefore, these findings suggest that PRIM2 variants p.Arg289His and p.Arg302Cys facilitate favourable conditions for carcinogenesis. Overall, this study provides in situ and in vitro data that demonstrates the pivotal role that population-specific PRIM2 variants may play in prostate cancer onset and progression in African-descent men.