Universität zu Köln

Worst, Thomas S., Weis, Cleo-Aron, Stoehr, Robert, Bertz, Simone, Eckstein, Markus, Otto, Wolfgang, Breyer, Johannes, Hartmann, Arndt, Bolenz, Christian, Wirtz, Ralph M. and Erben, Philipp ORCID: 0000-0002-8279-7636 (2018). CDKN2A as transcriptomic marker for muscle-invasive bladder cancer risk stratification and therapy decision-making. Sci Rep, 8. LONDON: NATURE PUBLISHING GROUP. ISSN 2045-2322

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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/f60/20) 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 CDKN2A(high) 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 (CDKN2A(high): 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 CDKN2A(high) 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 CDKN2A(high) poor prognosis group with low expression of drug target genes.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Worst, Thomas S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Weis, Cleo-Aron UNSPECIFIED UNSPECIFIED UNSPECIFIED Stoehr, Robert UNSPECIFIED UNSPECIFIED UNSPECIFIED Bertz, Simone UNSPECIFIED UNSPECIFIED UNSPECIFIED Eckstein, Markus UNSPECIFIED UNSPECIFIED UNSPECIFIED Otto, Wolfgang UNSPECIFIED UNSPECIFIED UNSPECIFIED Breyer, Johannes UNSPECIFIED UNSPECIFIED UNSPECIFIED Hartmann, Arndt UNSPECIFIED UNSPECIFIED UNSPECIFIED Bolenz, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Wirtz, Ralph M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Erben, Philipp UNSPECIFIED orcid.org/0000-0002-8279-7636 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-172472
DOI:	10.1038/s41598-018-32569-x
Journal or Publication Title:	Sci Rep
Volume:	8
Date:	2018
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	2045-2322
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language COMPREHENSIVE MOLECULAR CHARACTERIZATION; FREQUENT GENETIC ALTERATIONS; UROTHELIAL CARCINOMA; P16 EXPRESSION; FGFR3; P53; PAZOPANIB; SUBTYPES; CLASSIFICATION; IDENTIFICATION Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/17247