Eckstein, Markus and Wirtz, Ralph Markus and Gross-Weege, Matthias and Breyer, Johannes and Otto, Wolfgang and Stoehr, Robert and Sikic, Danijel and Keck, Bastian and Eidt, Sebastian and Burger, Maximilian and Bolenz, Christian and Nitschke, Katja and Porubsky, Stefan and Hartmann, Arndt and Erben, Philipp (2018) mRNA-Expression of KRT5 and KRT20 Defines Distinct Prognostic Subgroups of Muscle-Invasive Urothelial Bladder Cancer Correlating with Histological Variants. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 19 (11): 3396. ISSN 1661-6596, 1422-0067
Full text not available from this repository. (Request a copy)Abstract
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 (KRT5) and keratin 20 (KRT20). Reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) was applied to quantify gene expression of KRT5 and KRT20 using TaqMan (R)-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 KRT5 and low expression of KRT20 were associated with significantly improved recurrence-free survival (RFS) and disease-specific survival disease specific survival (DSS: 5-year DSS for KRT5 high: 58%; 5-year DSS for KRT20 high: 29%). KRT5 and KRT20 were associated with rates of lymphovascular invasion and lymphonodal metastasis. The combination of KRT5 and KRT20 allowed identification of patients with a very poor prognosis (KRT20(+)/KRT5(-), 5-year DSS 0%, p < 0.0001). In silico analysis of the independent MDACC cohorts revealed congruent results (5-year DSS for KRT20 low vs. high: 84% vs. 40%, p = 0.042). High KRT20-expressing tumors as well as KRT20(+)/KRT- tumors were significantly enriched with aggressive urothelial carcinoma variants (micropapillary, plasmacytoid, nested).
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | COMPREHENSIVE MOLECULAR CHARACTERIZATION; BREAST-CANCER; CARCINOMA; IDENTIFICATION; VALIDATION; RECURRENCE; CYSTECTOMY; PORTRAITS; PREDICTOR; SUBTYPES; Bladder cancer; muscle-invasive bladder cancer; molecular diagnostics; molecular subtyping; KRT5; KRT20 |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Urologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 10 Oct 2019 09:06 |
| Last Modified: | 10 Oct 2019 09:06 |
| URI: | https://pred.uni-regensburg.de/id/eprint/13598 |
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