CDKN2A as transcriptomic marker for muscle-invasive bladder cancer risk stratification and therapy decision-making

Journal article


Publication Details

Author(s): Worst TS, Weis CA, Stoehr R, Bertz S, Eckstein M, Otto W, Breyer J, Hartmann A, Bolenz C, Wirtz RM, Erben P
Journal: Scientific Reports
Publication year: 2018
Volume: 8
Journal issue: 1
ISSN: 2045-2322


Abstract

Deletions of the cell cycle control gene CDKN2A are described as progression markers of non-muscle invasive bladder cancer and to be associated with fibroblast growth factor 3 (FGFR3) mutations. The prognostic role of CDKN2A RNA expression in muscle invasive bladder cancer (MIBC) is under discussion. In 80 MIBC patients (m/f 60/20) who underwent radical cystectomy the expression of CDKN2A and FGFR3 was examined with qRT-PCR (test cohort). The MDA cohort (n = 57) and the TCGA cohort (n = 365) served for validation. The expression of drug target genes and TCGA molecular subtypes was correlated with CDKN2A expression. In the test cohort CDKN2Ahigh patients (n = 8; 10.0%) had a significantly shorter recurrence-free (p = 0.018) and disease-specific (p = 0.006) survival compared to the rest of the cohort. A similar stratification was seen in the validation cohorts (CDKN2Ahigh: n = 7, 12.3%, p = 0.001; n = 46, 12.6%, p = 0.011). In the TCGA cohort these patients had a comparably low expression of drug target genes. The expression of CDKN2A significantly differed among TGCA molecular subtypes. 71.7% of CDKN2Ahigh were TCGA basal squamous tumours but also show divergent molecular features compared to this group. In summary CDKN2A RNA expression-based risk stratification of MIBC allows the identification of a CDKN2Ahigh poor prognosis group with low expression of drug target genes.


FAU Authors / FAU Editors

Bertz, Simone PD Dr.
Pathologisches Institut
Eckstein, Markus Dr. med.
Pathologisches Institut
Hartmann, Arndt Prof. Dr. med.
Lehrstuhl für Allgemeine Pathologie und Pathologische Anatomie


External institutions with authors

STRATIFYER Molecular Pathology GmbH
Universität Regensburg
Universitätsklinikum Mannheim
Universität Ulm


How to cite

APA:
Worst, T.S., Weis, C.-A., Stoehr, R., Bertz, S., Eckstein, M., Otto, W.,... Erben, P. (2018). CDKN2A as transcriptomic marker for muscle-invasive bladder cancer risk stratification and therapy decision-making. Scientific Reports, 8(1). https://dx.doi.org/10.1038/s41598-018-32569-x

MLA:
Worst, Thomas S., et al. "CDKN2A as transcriptomic marker for muscle-invasive bladder cancer risk stratification and therapy decision-making." Scientific Reports 8.1 (2018).

BibTeX: 

Last updated on 2019-28-02 at 06:13