A valuable pair - candidate biomarkers RBM3 and PODXL in urothelial bladder cancer

Bladder cancer is a heterogenous disease, ranging from minimally invasive, low-grade tumours with lowrecurrence rates and mortality on one end of the spectrum, and muscle invasive, high-grade disease prone torecurrence, progression and death at the other end.The aim of this thesis was to investigate the expression, clinicopathological correlates and prognostic significanceof the candidate biomarkers podocalyxin-like protein (PODXL, papers II and III) and RNA-binding motif protein 3(RBM3, papers I, III and IV) in urothelial bladder cancer (UBC). In paper IV, the potential predictive significance ofRBM3 was also examined. The candidate biomarkers were examined alongside established clinical risk factors.RBM3 expression was evaluated by immunohistochemistry in tissue microarrays (TMA) from three differentpatient cohorts (n=343 in paper I, n=272 in paper III and n=151 in paper IV). In paper I, negative RBM3 expressionwas significantly associated with unfavourable tumour characteristics and was an independent predictor of shorterdisease-specific survival (DSS) as well as 5-year overall survial (OS). Patients with Ta/T1 tumours displayingnegative RBM3 expression had a significantly reduced 24 month progression-free survival (PFS) and 5-year OS.No association was seen between RBM3 expression and recurrence. In paper 3, these associations werevalidated, although with a somewhat different cut-off. Low RBM3 expression was significantly associated withunfavourable tumour characteristics and was an independent predictor of a shorter OS in both the full cohort andin T1 disease.In paper IV, the expression of RBM3 was evaluated in tumours from 151 patients treated with cystectomy due tomuscle-invasive UBC, 45.7% of which had received neoadjuvant chemotherapy (NAC). RBM3 expression was notprognostic in the full cohort. However, when accounting for NAC, there was a significantly reduced RFS in in thegroup of patients with high RBM3 expression who had not been treated compa