Proteomics

Dataset Information

0

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


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 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.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

DISEASE(S): Prostate Adenocarcinoma

SUBMITTER: Thilo Bracht  

LAB HEAD: Thilo Bracht

PROVIDER: PXD031847 | Pride | 2022-06-24

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
OEI24566.msf Msf
OEI24566.mzML Mzml
OEI24566.raw Raw
OEI24568.msf Msf
OEI24568.mzML Mzml
Items per page:
1 - 5 of 70
altmetric image

Publications

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

Csizmarik Anita A   Keresztes Dávid D   Nagy Nikolett N   Bracht Thilo T   Sitek Barbara B   Witzke Kathrin K   Puhr Martin M   Tornyi Ilona I   Lázár József J   Takács László L   Kramer Gero G   Sevcenco Sabina S   Maj-Hes Agnieszka A   Jurányi Zsolt Z   Hadaschik Boris B   Nyirády Péter P   Szarvas Tibor T  

International journal of cancer 20220621 8


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 liq  ...[more]

Similar Datasets

2023-08-28 | PXD038697 | Pride
2024-08-08 | GSE271075 | GEO
2023-01-01 | GSE220467 | GEO
2024-04-01 | GSE252216 | GEO
2024-04-01 | GSE252203 | GEO
2021-04-01 | GSE160393 | GEO
2020-03-26 | GSE127957 | GEO
2020-03-26 | GSE127241 | GEO
2020-03-26 | GSE126917 | GEO
2024-08-02 | GSE248619 | GEO