Differential Expression of Molecules that Contribute to the Pathogenesis of Bladder Pain Syndrome

Bladder Pain Syndrome (BPS) is a chronic, clinically heterogeneous condition characterised by pelvic pain and urinary urgency, yet it lacks reliable biomarkers and consistently effective treatments. Traditional classification systems—primarily based on cystoscopic findings such as Hunner lesions—do not adequately capture the underlying biological diversity. This thesis investigated whether transcriptomic profiling of bladder tissue could reveal molecular signatures associated with distinct BPS subtypes, thereby informing more targeted diagnostic and therapeutic approaches.
A systematic review of 20 molecular studies was first conducted to identify candidate genes and proteins implicated in BPS pathophysiology. These targets informed analysis of an in- house transcriptomic dataset derived from bladder biopsies of 13 clinically well-characterised female patients, encompassing both BPS and non-BPS cases. Expression data were interpreted in conjunction with cystoscopic findings, histology, trans-epithelial resistance, and O’Leary-Sant symptom scores.
Although differential gene expression between diagnostic groups was limited, individual- level analyses revealed transcriptional variability suggestive of biologically meaningful subtypes. Two samples (Y2336, Y2338) exhibited prominent immune activation—including elevated IL6, TNF, CCL2, and STAT1/3—despite differing cystoscopic phenotypes. A third case (Y2610) displayed high CNR1 expression with minimal inflammatory signalling, consistent with a neuroplasticity-associated profile. Most remaining samples showed muted or heterogeneous expression patterns, potentially reflecting biologically quiescent states, unprofiled mechanisms, or sampling limitations.
These findings provide preliminary support for a stratified model of BPS, including immune- enriched, neurogenic, and oxidative stress–linked subtypes. The heterogeneity observed cautions against population-averaged interpretations and highlights the potential of personalised transcriptomic analysis. This thesis contributes novel data toward molecular characterisation of BPS and sets the stage for future multi-omics studies in larger cohorts. Refining such subtype frameworks could ultimately improve biomarker development and guide personalised management in chronic bladder pain.