PXD030924

PXD030924 is an original dataset announced via ProteomeXchange.

Title	Protein profiling of WERI RB1 and etoposide resistant WERI ETOR reveals new insights to overcome topoisomerase inhibitor resistance in retinoblastoma
Description	Chemotherapy resistance is one of the reasons for the loss of the eye in retinoblastoma (RB) pa-tients. RB chemotherapy resistance has been investigated in different cell culture models like WERI RB1. Furthermore, chemotherapy resistant RB subclones like the etoposide resistant WERI ETOR cell line have been established to improve understanding of chemotherapy resistance in RB. Ob-jective of this study was to characterize the cell line models of an etoposide sensitive WERI RB1 and its etoposide resistant subclone WERI ETOR by proteomics analysis. Subsequently, quantitative proteomic data served for correlation analysis with known drug perturbation profiles. . WERI RB1 and WERI ETOR were cultured and prepared for quantitative mass spectrometry. Comparative proteomic profiling was performed with electrospray ionization tandem mass spectrometry in data-independent acquisition mode (SWATH). The raw SWATH files were processed using neural networks in library free mode along with machine learning algorithms. Pathway enrichment was performed using the REACTOME pathway resource and correlated to the Molecular Signature Database (MSigDB) hallmark gene set collections for functional annotation. Also, a drug connec-tivity analysis using the L1000 database was used to correlate the mechanism-of-action (MOA) for different anticancer reagents to WERI RB1 / WERI ETOR signatures. A total 4,756 proteins were identified across all samples which revealed a distinct clustering between groups. Of these pro-teins, 64 proteins were significantly altered (q < 0.05 & log2FC |>2|, 22% higher in WERI ETOR). Pathway analysis showed an enriched metabolic pathway for retinoid metabolism and transport pathway in WERI ETOR and for sphingolipid de novo biosynthesis in WERI RB1. In addition, this study showed similar protein signatures of topoisomerase inhibitors and WERI ETOR as well as of ATPase inhibitors, acetylcholine receptor antagonists and VEGFR inhibitors and WERI RB1. In this study, WERI RB1 and WERI ETOR were characterized as a cell line model for chemotherapy re-sistance in RB by using data-independent mass spectrometry. The global proteome revealed the activation of sphingolipid de novo biosynthesis in WERI RB1 and potential treatment options for etoposide resistant RB.
HostingRepository	PRIDE
AnnounceDate	2022-05-20
AnnouncementXML	Submission_2022-05-20_05:16:35.234.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Thorben Sauer
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	TripleTOF 5600

Revision	Datetime	Status	ChangeLog Entry
0	2022-01-13 01:33:15	ID requested
⏵ 1	2022-05-20 05:16:37	announced

Kakkassery V, Gemoll T, Kraemer MM, Sauer T, Tura A, Ranjbar M, Grisanti S, Joachim SC, Mergler S, Reinhard J, Protein Profiling of WERI-RB1 and Etoposide-Resistant WERI-ETOR Reveals New Insights into Topoisomerase Inhibitor Resistance in Retinoblastoma. Int J Mol Sci, 23(7):(2022) [pubmed]

submitter keyword: chemotherapy resistance, mass spectrometry, retinoblastoma, WERI ETOR, WERI RB1

Timo Gemoll
contact affiliation	Section for Translational Surgical Oncology and Biobanking, Department of Surgery, University of Luebeck & and University Hospital Clinic Schleswig-Holstein
contact email	timo.gemoll@uni-luebeck.de
lab head
Thorben Sauer
contact affiliation	Section for translational surgical oncology and biobanking
contact email	thorben.sauer@student.uni-luebeck.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/05/PXD030924

PRIDE project URI

• PRIDE
  1. PXD030924
     1. Label: PRIDE project
     2. Name: Protein profiling of WERI RB1 and etoposide resistant WERI ETOR reveals new insights to overcome topoisomerase inhibitor resistance in retinoblastoma