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:
CreatorsEmailORCIDORCID Put Code
Worst, Thomas S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weis, Cleo-AronUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stoehr, RobertUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bertz, SimoneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eckstein, MarkusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Otto, WolfgangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Breyer, JohannesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hartmann, ArndtUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bolenz, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wirtz, Ralph M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Erben, PhilippUNSPECIFIEDorcid.org/0000-0002-8279-7636UNSPECIFIED
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:
KeywordsLanguage
COMPREHENSIVE MOLECULAR CHARACTERIZATION; FREQUENT GENETIC ALTERATIONS; UROTHELIAL CARCINOMA; P16 EXPRESSION; FGFR3; P53; PAZOPANIB; SUBTYPES; CLASSIFICATION; IDENTIFICATIONMultiple languages
Multidisciplinary SciencesMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/17247

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