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

Eckstein M, Wirtz RM, Gross-Weege M, Breyer J, Otto W, Stoehr R, Sikic D, Keck B, Eidt S, Burger M, Bolenz C, Nitschke K, Porubsky S, Hartmann A, Erben P (2018)

Publication Type: Journal article

Publication year: 2018

Journal

International Journal of Molecular Sciences MDPI

Book Volume: 19

Journal Issue: 11

DOI: 10.3390/ijms19113396

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).

Authors with CRIS profile

Markus Eckstein Institute of Pathology Bastian Keck Medizinische Fakultät Arndt Hartmann Lehrstuhl für Allgemeine Pathologie und Pathologische Anatomie

Involved external institutions

Ruprecht-Karls-Universität Heidelberg DE Germany (DE) Universität Regensburg DE Germany (DE) Universität Ulm DE Germany (DE) STRATIFYER Molecular Pathology GmbH DE Germany (DE) St. Elisabeth-Krankenhaus Köln-Hohenlind DE Germany (DE)

How to cite

APA:

Eckstein, M., Wirtz, R.M., Gross-Weege, M., Breyer, J., Otto, W., Stoehr, R.,... Erben, P. (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). https://doi.org/10.3390/ijms19113396

MLA:

Eckstein, Markus, et al. "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 (2018).

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