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

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.

• Authors: 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
• Journal: Scientific reports (Sci Rep) Vol. 8 Issue 1 Pg. 14383 (09 26 2018) ISSN: 2045-2322 [Electronic] England
• PMID: 30258198 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• CDKN2A protein, human
• Cyclin-Dependent Kinase Inhibitor p16
• RNA, Messenger

Topics

• Adult
• Aged
• Aged, 80 and over
• Biomarkers, Tumor (genetics)
• Cyclin-Dependent Kinase Inhibitor p16 (genetics)
• Female
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Humans
• Male
• Middle Aged
• Muscle Neoplasms (diagnosis, genetics, pathology, secondary)
• Neoplasm Invasiveness (diagnosis, genetics, pathology)
• Prognosis
• RNA, Messenger (genetics)
• Transcriptome
• Urinary Bladder Neoplasms (diagnosis, genetics, pathology)