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Lookup NU author(s): Dr Christoph OingORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2022, The Author(s). Purpose: Advanced testicular germ cell tumours (GCT) generally have a good prognosis owing to their unique sensitivity towards cisplatin-based chemotherapies. However, cisplatin-resistant GCT have a poor outcome. Further studies are mandatory to better understand resistance mechanisms and develop therapeutic strategies for refractory GCTs. Methods: Protein levels in cisplatin-resistant GCT cell lines of NTERA-2, NCCIT and 2102EP were analyzed by quantitative proteomic mass spectrometry (MS) in combination with stable isotope labelling by amino acids in cell culture (SILAC). Differentially abundant protein markers of acquired cisplatin resistance were validated by Western blotting. Comprehensive bioinformatical annotation using gene set enrichment analyses (GSEA) and STRING interaction analysis were performed to identify commonly affected pathways in cisplatin resistance and the data were compared to the GCT cohort of the ‘The Cancer Genome Atlas’. Results: A total of 4375 proteins were quantified by MS, 144 of which were found to be differentially abundant between isogenic resistant and sensitive cell line pairs (24 proteins for NTERA-2, 60 proteins for NCCIT, 75 proteins for 2102EP). Western blotting confirmed regulation of key resistance-associated proteins (CBS, ANXA1, LDHA, CTH, FDXR). GSEA revealed a statistically significant enrichment of DNA repair-associated proteins in all three resistant cell lines and specific additional processes for individual cell lines. Conclusion: High resolution MS combined with SILAC is a powerful tool and 144 significantly deregulated proteins were found in cisplatin-resistant GCT cell lines. Our study provides the largest proteomic in vitro library for cisplatin resistance in GCT, yet, enabling further studies to develop new treatment options for patients with refractory GCT.
Author(s): Fichtner A, Bohnenberger H, Elakad O, Richter A, Lenz C, Oing C, Strobel P, Kueffer S, Nettersheim D, Bremmer F
Publication type: Article
Publication status: Published
Journal: World Journal of Urology
Year: 2022
Volume: 40
Issue: 2
Pages: 373-383
Print publication date: 01/02/2022
Online publication date: 27/01/2022
Acceptance date: 07/01/2022
Date deposited: 24/07/2024
ISSN (print): 0724-4983
ISSN (electronic): 1433-8726
Publisher: Springer Science and Business Media Deutschland GmbH
URL: https://doi.org/10.1007/s00345-022-03936-1
DOI: 10.1007/s00345-022-03936-1
Data Access Statement: The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE [59] partner repository with the dataset identifier PXD030251. All other data is available on request from the corresponding author.
PubMed id: 35084545
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