PXD031847-1

PXD031847 is an original dataset announced via ProteomeXchange.

Title	Proteome profiling of enzalutamide-resistant cell lines and serum analysis identified ALCAM as marker of resistance in castration-resistant prostate cancer
Description	Enzalutamide (ENZA) is a frequently used therapy in metastatic castration-resistant prostate cancer (mCRPC). Baseline or acquired resistance to ENZA have been observed, but the molecular mechanisms of resistance are poorly understood. We aimed to identify proteins involved in ENZA resistance and to find therapy-predictive serum markers. We performed comparative proteome analyses on ENZA-sensitive parental (LAPC4, DUCAP) and -resistant prostate cancer cell lines (LAPC4-ENZA, DUCAP-ENZA) using liquid chromatography tandem mass spectrometry (LC-MS/MS). The most promising 4 marker candidates were selected using bioinformatic approaches. Serum concentrations of selected markers (ALCAM, AGR2, NDRG1, IDH1) were measured in 72 ENZA-treated mCRPC patients’ samples using ELISA. In addition, ALCAM serum levels were measured in 101 Abiraterone (ABI) and 100 Docetaxel (DOC)-treated mCRPC patients. Results were correlated with clinical and follow-up data. The functional role of ALCAM in ENZA resistance was assessed in vitro using siRNA. Our proteome analyses revealed 731 significantly differentially abundant proteins between ENZA-sensitive and -resistant cells and our filtering methods identified 4 biomarker candidates. Serum analyses of these proteins revealed only ALCAM to be associated with poor patient survival. Furthermore, higher baseline ALCAM levels were associated with poor survival in ABI- but not in DOC-treated patients. In LAPC4-ENZA resistant cells, ALCAM silencing by siRNA knockdown resulted in significantly enhanced ENZA sensitivity. Our analyses revealed that ALCAM serum levels may help to identify ENZA- and ABI-resistant patients and may thereby help to optimize future clinical decision-making. Our functional analyses suggest the possible involvement of ALCAM in ENZA resistance.
HostingRepository	PRIDE
AnnounceDate	2022-06-24
AnnouncementXML	Submission_2022-06-24_09:51:35.652.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Thilo Bracht
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2022-02-23 05:43:42	ID requested
⏵ 1	2022-06-24 09:51:36	announced

Csizmarik A, Keresztes D, Nagy N, Bracht T, Sitek B, Witzke K, Puhr M, Tornyi I, L, á, z, á, r J, Tak, á, cs L, Kramer G, Sevcenco S, Maj-Hes A, Jur, á, nyi Z, Hadaschik B, Nyir, á, dy P, Szarvas T, Proteome profiling of enzalutamide-resistant cell lines and serum analysis identified ALCAM as marker of resistance in castration-resistant prostate cancer. Int J Cancer, 151(8):1405-1419(2022) [pubmed]

submitter keyword: prostate cancer, enzalutamide, secondary resistance

Thilo Bracht
contact affiliation	Clinical Proteomics Medizinisches Proteom-Center Ruhr-University Bochum
contact email	thilo.bracht@rub.de
lab head
Thilo Bracht
contact affiliation	Clinical Proteomics
contact email	thilo.bracht@rub.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD031847
     1. Label: PRIDE project
     2. Name: Proteome profiling of enzalutamide-resistant cell lines and serum analysis identified ALCAM as marker of resistance in castration-resistant prostate cancer