title: Podocalyxin-like and RNA-binding motif protein 3 are prognostic biomarkers in urothelial bladder cancer: a validatory study.
abstract: BACKGROUND
  Urothelial bladder cancer (UBC) is a disease that often is discovered when the tumour is non-muscle invasive, i.e. in Ta or T1 stage. Some patients will progress into muscle-invasive disease, a potentially deadly condition. Although there are some prognostic models, the need for prognostic and predictive biomarkers is considerate and urgent. Membranous expression of podocalyxin-like protein 1 (PODXL) and low expression of the RNA-binding motif 3 (RBM3) has previously been shown to be associated with an aggressive tumour phenotype and poor prognosis in several forms of cancer, including UBC. In this study, we sought to validate the prognostic impact of PODXL and RBM3 in an independent cohort of UBC.
  
  
  METHODS
  Using tissue microarrays and immunohistochemistry, PODXL and RBM3 expression was evaluated in 272 incident UBC cases from the prospective, population-based cohort study Malmö Diet and Cancer. Kaplan-Meier analysis and Cox proportional hazards modelling were used to evaluate the prognostic impact of these markers on 5-year overall survival (OS).
  
  
  RESULTS
  In line with previous studies, both membranous PODXL expression and low RBM3 expression was significantly associated with disadvantageous clinicopathological features. Membranous PODXL expression was significantly associated with a reduced 5-year overall survival in the entire cohort (univariable HR 3.28; 95% CI 1.89-5.69), but this association did not remain significant in multivariable analysis. In T1 tumours, PODXL was significantly associated with reduced survival in univariable analysis (HR = 2.83; 95% CI 1.04-7.72) and borderline significant in multivariable analysis (HR = 2.60; 95% CI 0.91-7.39). Low RBM3 expression was an independent predictor of a reduced survival in the entire cohort (univariable HR 3.19; 95% CI 2.02-5.04, and multivariable HR 1.85; 95% CI 1.11-3.09), and in T1 tumours (univariable HR 2.64; 95% CI 1.11-6.27, and multivariable HR 2.63; 95% CI 1.01-6.84).
  
  
  CONCLUSIONS
  A link between membranous PODXL expression and clinically more aggressive tumours was further confirmed, but PODXL expression was not an independent prognostic biomarker in this study. Low RBM3 expression was validated as an independent factor of poor prognosis in UBC, including T1 disease. These findings suggest that these biomarkers could be useful in stratifying patients with non-muscle invasive disease for more aggressive first line treatment.
authors.affiliation: Department of Clinical Sciences Lund, Division of Oncology and Pathology, Lund University, Lund, Sweden.
authors.forename: Karolina
authors.identifier: 0000-0002-6204-9681
authors.initials: K
authors.lastname: Boman
authors.affiliation: Department of Clinical Sciences Lund, Division of Oncology and Pathology, Lund University, Lund, Sweden.
authors.forename: Gustav
authors.initials: G
authors.lastname: Andersson
authors.affiliation: Department of Clinical Sciences Lund, Division of Oncology and Pathology, Lund University, Lund, Sweden.
authors.forename: Christoffer
authors.initials: C
authors.lastname: Wennersten
authors.affiliation: Department of Clinical Sciences Lund, Division of Oncology and Pathology, Lund University, Lund, Sweden.
authors.forename: Björn
authors.initials: B
authors.lastname: Nodin
authors.affiliation: Department of Translational Medicine, Lund University, Malmö, Sweden.|Department of Urology, Skåne University Hospital, Malmö, Sweden.
authors.forename: Göran
authors.initials: G
authors.lastname: Ahlgren
authors.affiliation: Department of Clinical Sciences Lund, Division of Oncology and Pathology, Lund University, Lund, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Jirström
keywords: Bladder cancer; PODXL; Prognosis; RBM3