A three-gene methylation marker panel for the nodal metastatic risk assessment of muscle-invasive bladder cancer

Journal article


Publication Details

Author(s): Stubendorff B, Wilhelm K, Posselt K, Catto J, Hartmann A, Bertz S, Fuessel S, Novotny V, Toma M, Gajda M, Lehmann J, Wunderlich H, Grimm MO, Stoeckle M, Junker K
Journal: Journal of Cancer Research and Clinical Oncology
Publication year: 2019
Volume: 145
Journal issue: 4
Pages range: 811-820
ISSN: 0171-5216


Abstract

PurposeIn this study, we aimed to identify a DNA methylation pattern suitable for prognosis assessment of muscle-invasive bladder cancer and to investigate metastasis-associated processes regulated by DNA methylation.MethodsGenome-wide methylation analysis was performed on 23 muscle-invasive bladder tumors by microarray analysis. Validation was performed by the qAMP technique in two different patient cohorts (n=32 and n=100). mRNA expression was analyzed in 12 samples. Protein expression was determined using tissue microarrays of 291 patients. Bladder cancer cell lines T24 and 253JB-V were used for functional analyses.ResultsMicroarray analyses revealed KISS1R, SEPT9 and CSAD as putative biomarkers with hypermethylation in node-positive tumors. The combination of the three genes predicted the metastatic risk with sensitivity of 73% and specificity of 71% in cohort 1, and sensitivity of 82% and specificity of 54% in cohort 2. mRNA expression differences were detected for KISS1R (p=0.04). Protein expression of KISS1R was significantly reduced (p<0.001). Knockdown of SEPT9v3 resulted in increased cell migration by 28% (p=0.04) and increased invasion by 22% (p=0.004). KISS1R overexpression resulted in decreased cell migration (25%, p=0.1).ConclusionsWe identified a methylation marker panel suitable to differentiate between patients with positive and negative lymph nodes at time of cystectomy. This enables a risk assessment for patients who potentially benefit from extended lymph node resection as well as from neoadjuvant chemotherapy and could improve the survival rates. Furthermore, we examined the impact of putative markers on tumor behavior. Hence, KISS1R and SEPT9 could represent a starting point for the development of novel therapy approaches.


FAU Authors / FAU Editors

Bertz, Simone PD Dr.
Pathologisches Institut
Hartmann, Arndt Prof. Dr. med.
Lehrstuhl für Allgemeine Pathologie und Pathologische Anatomie


External institutions
St. Georg Klinikum Eisenach gemeinnützige GmbH
Technische Universität Dresden
Universität des Saarlandes (UdS)
Universitätsklinikum Jena
University of Sheffield


How to cite

APA:
Stubendorff, B., Wilhelm, K., Posselt, K., Catto, J., Hartmann, A., Bertz, S.,... Junker, K. (2019). A three-gene methylation marker panel for the nodal metastatic risk assessment of muscle-invasive bladder cancer. Journal of Cancer Research and Clinical Oncology, 145(4), 811-820. https://dx.doi.org/10.1007/s00432-018-02829-4

MLA:
Stubendorff, Beatrice, et al. "A three-gene methylation marker panel for the nodal metastatic risk assessment of muscle-invasive bladder cancer." Journal of Cancer Research and Clinical Oncology 145.4 (2019): 811-820.

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Last updated on 2019-15-04 at 19:08