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
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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