Evidence map›Paper›PMID 35689436›Full record

ArticleInternational journal of cancer2022

Proteome profiling of enzalutamide-resistant cell lines and serum analysis identified ALCAM as marker of resistance in castration-resistant prostate cancer.

Anita Csizmarik, Dávid Keresztes, Nikolett Nagy, Thilo Bracht, Barbara Sitek, Kathrin Witzke, Martin Puhr, Ilona Tornyi, József Lázár, László Takács and 7 more

Open access · hybridAbstract read
In one paragraph

Article in International journal of cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.6field-weighted citation impact, top 32% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 4 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors at 7 institutions in 3 countries.

Anita CsizmarikDepartment of Urology, Semmelweis University, Budapest, Hungary.ORCID 0000-0001-8394-3722
Dávid KeresztesDepartment of Urology, Semmelweis University, Budapest, Hungary.ORCID 0000-0003-2011-8316
Nikolett NagyDepartment of Urology, Semmelweis University, Budapest, Hungary.
Thilo BrachtMedizinisches Proteom Center, Ruhr University Bochum, Bochum, Germany.
Barbara SitekMedizinisches Proteom Center, Ruhr University Bochum, Bochum, Germany.
Kathrin WitzkeMedizinisches Proteom Center, Ruhr University Bochum, Bochum, Germany.
Martin PuhrDepartment of Urology, Medical University of Innsbruck, Innsbruck, Austria.
Ilona TornyiDepartment of Human Genetics, University of Debrecen, Debrecen, Hungary.
József LázárBiosystems International Kft, Debrecen, Hungary.
László TakácsDepartment of Human Genetics, University of Debrecen, Debrecen, Hungary.
Gero KramerDepartment of Urology, Medical University of Vienna, Vienna, Austria.
Sabina SevcencoDepartment of Urology, Medical University of Vienna, Vienna, Austria.
Agnieszka Maj-HesDepartment of Urology, Medical University of Vienna, Vienna, Austria.
Zsolt JurányiDepartment of Radiobiology and Diagnostic Onco-Cytogenetics, Center of Radiotherapy, National Institute of Oncology, Budapest, Hungary.
Boris HadaschikDepartment of Urology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Péter NyirádyDepartment of Urology, Semmelweis University, Budapest, Hungary.
Tibor SzarvasDepartment of Urology, Semmelweis University, Budapest, Hungary.ORCID 0000-0002-6321-0799
Semmelweis University · HUMedical University of Vienna · ATUniversity Hospitals of the Ruhr-University of Bochum · DEUniversity of Debrecen · HUEssen University Hospital · DEInnsbruck Medical University · ATNational Institute of Oncology · HU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

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 top four most promising candidate markers were selected using bioinformatic approaches. Serum concentrations of selected markers (ALCAM, AGR2, NDRG1, IDH1) were measured in pretreatment samples of 72 ENZA-treated mCRPC patients using ELISA. In addition, ALCAM serum levels were measured in 101 Abiraterone (ABI) and 100 Docetaxel (DOC)-treated mCRPC patients' baseline samples. 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 four 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.

Indexed as

Activated-Leukocyte Cell Adhesion MoleculeCell Adhesion Molecules, NeuronalDrug Resistance, NeoplasmProstatic Neoplasms, Castration-ResistantAntigens, CDBenzamidesCell LineChromatography, LiquidDocetaxelFetal ProteinsHumansMaleNitrilesPhenylthiohydantoinProstate-Specific AntigenProteomeActivated-Leukocyte Cell Adhesion MoleculeALCAM protein, humanAntigens, CDBenzamidesCell Adhesion Molecules, NeuronalDocetaxelenzalutamideFetal ProteinsNitrilesPhenylthiohydantoinProstate-Specific AntigenProteomeRNA, Small InterferingALCAMbiomarkerenzalutamideprostate cancerproteome analysis

Identifiers

PMID35689436
PMCPMC9539937
OpenAlexW4282925319

What OpenQuestion holds

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LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.