Subclassification, survival prediction and drug target analyses of chemotherapy-naïve muscle-invasive bladder cancer with a molecular screening

Journal article


Publication Details

Author(s): Rinaldetti S, Rempel E, Worst TS, Eckstein M, Steidler A, Weiss CA, Bolenz C, Hartmann A, Erben P
Journal: Oncotarget
Publication year: 2018
Volume: 9
Journal issue: 40
Pages range: 25935-25945
ISSN: 1949-2553


Abstract

Background: Transcriptome expression studies identified distinct muscle invasive bladder cancer (MIBC) subtypes closely related with breast cancer subclasses. Here we developed a sensitive quantification method for MIBC subclassification (luminal, basal, p53-like). In addition, the subtype specific expression of drug targets has been investigated.
Methods: Absolute quantification (nCounter) of a 64-gene panel was performed on MIBC patients (n=47) treated exclusively with radical cystectomy (RC). In conjunction of 170 MIBCs from 3 independent cohorts, a minimal set of consensus genes has been established. Survival of the consensus subtypes has been assessed by multivariate analysis. Relevant drug targets were tested for their subtype specificity in a clustering independent assessment.
Results: A reduced 36-gene panel stably clustered into 3 subtypes throughout the cohorts (luminal, basal, infiltrated). Patients treated by RC only, showed worst 8-year disease specific survival (DSS) for the luminal subtype in contrast to the infiltrated subtype (17% vs. 73%, p=0.011). In multivariate analyses, the risk stratification based on luminal versus not-luminal MIBC proved to be an independent predictor for DSS superior to the TNM system in patients with RC. Drug targets (e.g. ERBB2, FGFR, AR, PDGFRB) showed a distinct subtype attribution. The subtypes based on this nCounter screening could further be validated by the TCGA cohort.
Conclusion: This MIBC subtype screening predicted survival and allowed an analysis of subtype specific drug targets, thus being a powerful tool for the translation of personalized MIBC treatment concepts.


FAU Authors / FAU Editors

Eckstein, Markus Dr. med.
Pathologisches Institut
Hartmann, Arndt Prof. Dr. med.
Lehrstuhl für Allgemeine Pathologie und Pathologische Anatomie


External institutions with authors

Deutsches Krebsforschungszentrum (DKFZ)
Ruprecht-Karls-Universität Heidelberg
Universitätsklinikum Mannheim
Universität Ulm


How to cite

APA:
Rinaldetti, S., Rempel, E., Worst, T.S., Eckstein, M., Steidler, A., Weiss, C.A.,... Erben, P. (2018). Subclassification, survival prediction and drug target analyses of chemotherapy-naïve muscle-invasive bladder cancer with a molecular screening. Oncotarget, 9(40), 25935-25945. https://dx.doi.org/10.18632/oncotarget.25407

MLA:
Rinaldetti, Sebastien, et al. "Subclassification, survival prediction and drug target analyses of chemotherapy-naïve muscle-invasive bladder cancer with a molecular screening." Oncotarget 9.40 (2018): 25935-25945.

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Last updated on 2019-25-04 at 14:57