mRNA-Expression of KRT5 and KRT20 Defines Distinct Prognostic Subgroups of Muscle-Invasive Urothelial Bladder Cancer Correlating with Histological Variants

Recently, muscle-invasive bladder cancer (MIBC) has been subclassified by gene expression profiling, with a substantial impact on therapy response and patient outcome. We tested whether these complex molecular subtypes of MIBC can be determined by mRNA detection of keratin 5 ( ) and keratin 20 ( ). Reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) was applied to quantify gene expression of and using TaqMan -based assays in 122 curatively treated MIBC patients (median age 68.0 years). Furthermore, in silico analysis of the MD Anderson Cancer Center (MDACC) cohort (GSE48277 + GSE47993) was performed. High expression of and low expression of were associated with significantly improved recurrence-free survival (RFS) and disease-specific survival disease specific survival (DSS: 5-year DSS for high: 58%; 5-year DSS for high: 29%). and were associated with rates of lymphovascular invasion and lymphonodal metastasis. The combination of and allowed identification of patients with a very poor prognosis ( ⁺/ , 5-year DSS 0%, < 0.0001). In silico analysis of the independent MDACC cohorts revealed congruent results (5-year DSS for low vs. high: 84% vs. 40%, = 0.042). High -expressing tumors as well as ⁺/ tumors were significantly enriched with aggressive urothelial carcinoma variants (micropapillary, plasmacytoid, nested).