mRNA-expression of KRT5 and KRT20 defines distinct prognostic subgroups of muscle-invasive urothelial bladder cancer correlating with histological variants

• Verfasst von: Eckstein, Markus [VerfasserIn]
• Verfasst von: Groß-Weege, Matthias [VerfasserIn]
• Verfasst von: Nitschke, Katja [VerfasserIn]
• Verfasst von: Porubský, Štefan [VerfasserIn]
• Verfasst von: Erben, Philipp [VerfasserIn]
• Titel: mRNA-expression of KRT5 and KRT20 defines distinct prognostic subgroups of muscle-invasive urothelial bladder cancer correlating with histological variants
• Verf.angabe: Markus Eckstein, Ralph Markus Wirtz, Matthias Gross-Weege, Johannes Breyer, Wolfgang Otto, Robert Stoehr, Danijel Sikic, Bastian Keck, Sebastian Eidt, Maximilian Burger, Christian Bolenz, Katja Nitschke, Stefan Porubsky, Arndt Hartmann and Philipp Erben
• E-Jahr: 2018
• Jahr: 30 October 2018
• Umfang: 14 S.
• Fussnoten: Gesehen am 06.12.2018
• Titel Quelle: Enthalten in: International journal of molecular sciences
• Ort Quelle: Basel : Molecular Diversity Preservation International, 2000
• Jahr Quelle: 2018
• Band/Heft Quelle: 19(2018), 11, Artikel-ID 3396, Seite 1-14
• ISSN Quelle: 1422-0067
• ISSN Quelle: 1661-6596
• DOI: doi:10.3390/ijms19113396
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: <i>KRT20</i>
• Sach-SW: <i>KRT5</i>
• Sach-SW: Bladder cancer
• Sach-SW: molecular diagnostics
• Sach-SW: molecular subtyping
• Sach-SW: muscle-invasive bladder cancer
• K10plus-PPN: 1584918969
• K10plus-PPN:
  Universitätsbibliothek
• Lokale URL UB: Zum Volltext

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®-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).