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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| Hauptverfasser: | , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
26 September 2018
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| In: |
Scientific reports
Year: 2018, Jahrgang: 8 |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-018-32569-x |
| Online-Zugang: | 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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| Verfasserangaben: | 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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| 520 | |a 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. | ||
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