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

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...

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Main Authors: Worst, Thomas (Author) , Weis, Cleo-Aron Thias (Author) , Erben, Philipp (Author)
Format: Article (Journal)
Language:English
Published: 26 September 2018
In: Scientific reports
Year: 2018, Volume: 8
ISSN:2045-2322
DOI:10.1038/s41598-018-32569-x
Online Access:Verlag, kostenfrei, Volltext: http://dx.doi.org/10.1038/s41598-018-32569-x
Verlag, kostenfrei, Volltext: https://www.nature.com/articles/s41598-018-32569-x
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Author Notes:Thomas S. Worst, Cleo-Aron Weis, Robert Stöhr, Simone Bertz, Markus Eckstein, Wolfgang Otto, Johannes Breyer, Arndt Hartmann, Christian Bolenz, Ralph M. Wirtz & Philipp Erben
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Summary: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.
Item Description:Gesehen am 10.10.2018
Physical Description:Online Resource
ISSN:2045-2322
DOI:10.1038/s41598-018-32569-x

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