RNA Expression of DNA Damage Response Genes in Muscle-Invasive Bladder Cancer: Influence on Outcome and Response to Adjuvant Cisplatin-Based Chemotherapy
Autor: | Thomas Stefan Worst, Cleo-Aron Weis, Helena Schmidt, Jost von Hardenberg, Maurice Stephan Michel, Jonas Herrmann, Katja Nitschke, Philipp Erben, Philipp Nuhn |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
Male
0301 basic medicine Oncology ERCC6 medicine.medical_treatment cisplatin 0302 clinical medicine Biology (General) Spectroscopy Aged 80 and over BRCA1 Protein General Medicine Middle Aged Computer Science Applications BRCA1 adjuvant chemotherapy Chemistry Chemotherapy Adjuvant ERCC2 muscle-invasive bladder cancer 030220 oncology & carcinogenesis Cohort Female BRCA2 medicine.drug Adult medicine.medical_specialty BCL2 FOXM1 QH301-705.5 Antineoplastic Agents RAD50 Catalysis Article Inorganic Chemistry Cystectomy 03 medical and health sciences Internal medicine Biomarkers Tumor medicine Humans Neoplasm Invasiveness Physical and Theoretical Chemistry Molecular Biology QD1-999 Aged BRCA2 Protein Cisplatin Chemotherapy Bladder cancer business.industry Forkhead Box Protein M1 Organic Chemistry DNA-damage response RAD52 medicine.disease 030104 developmental biology Urinary Bladder Neoplasms RAD51 business DNA Damage |
Zdroj: | International Journal of Molecular Sciences International Journal of Molecular Sciences, Vol 22, Iss 4188, p 4188 (2021) Volume 22 Issue 8 |
ISSN: | 1422-0067 |
Popis: | Background: Perioperative cisplatin-based chemotherapy (CBC) can improve the outcome of patients with muscle-invasive bladder cancer (MIBC), but it is still to be defined which patients benefit. Mutations in DNA damage response genes (DDRG) can predict the response to CBC. The value of DDRG expression as a marker of CBC treatment effect remains unclear. Material and methods: RNA expression of the nine key DDRG (BCL2, BRCA1, BRCA2, ERCC2, ERCC6, FOXM1, RAD50, RAD51, and RAD52) was assessed by qRT-PCR in a cohort of 61 MICB patients (median age 66 y, 48 males, 13 females) who underwent radical cystectomy in a tertiary care center. The results were validated in the The Cancer Genome Atlas (TCGA) cohort of MIBC (n = 383). Gene expression was correlated with disease-free survival (DFS) and overall survival (OS). Subgroup analyses were performed in patients who received adjuvant cisplatin-based chemotherapy (ACBC) (Mannheim n = 20 and TCGA n = 75). Results: Low expression of RAD52 was associated with low DFS in both the Mannheim and the TCGA cohorts (Mannheim: p = 0.039 TCGA: p = 0.017). This was especially apparent in subgroups treated with ACBC (Mannheim: p = 0.0059 TCGA: p = 0.012). Several other genes showed an influence on DFS in the Mannheim cohort (BRCA2, ERCC2, FOXM1) where low expression was associated with poor DFS (p < 0.05 for all). This finding was not fully supported by the data in the TCGA cohort, where high expression of FOXM1 and BRCA2 correlated with poor DFS. Conclusion: Low expression of RAD52 correlated with decreased DFS in the Mannheim and the TCGA cohort. This effect was especially pronounced in the subset of patients who received ACBC, making it a promising indicator for response to ACBC on the level of gene expression. |
Databáze: | OpenAIRE |
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