2. Academic Validation
  3. Comparative proteome and serum analysis identified FSCN1 as a marker of abiraterone resistance in castration-resistant prostate cancer

Comparative proteome and serum analysis identified FSCN1 as a marker of abiraterone resistance in castration-resistant prostate cancer

  • Prostate Cancer Prostatic Dis. 2023 Aug 26. doi: 10.1038/s41391-023-00713-y.
Anita Csizmarik # 1,  Nikolett Nagy # 1,  Dávid Keresztes 1 2,  Melinda Váradi 1,  Thilo Bracht 3 4 5,  Barbara Sitek 3 4 5,  Kathrin Witzke 3 5,  Martin Puhr 6,  Ilona Tornyi 7,  József Lázár 7,  László Takács 7 8,  Gero Kramer 9,  Sabina Sevcenco 9,  Agnieszka Maj-Hes 9,  Boris Hadaschik 10,  Péter Nyirády 1,  Tibor Szarvas 11 12
Affiliations

Affiliations

  • 1 Department of Urology, Semmelweis University, Budapest, Hungary.
  • 2 Department of Molecular Biology, Semmelweis University, Budapest, Hungary.
  • 3 Medizinisches Proteom-Center, Ruhr University Bochum, Bochum, Germany.
  • 4 Department of Anesthesia, Intensive Care Medicine and Pain Therapy, University Hospital Knappschaftskrankenhaus Bochum, Bochum, Germany.
  • 5 Center for Protein Diagnostics, Medical Proteome Analysis, Ruhr-University Bochum, Bochum, Germany.
  • 6 Department of Urology, Medical University of Innsbruck, Innsbruck, Austria.
  • 7 Department of Human Genetics, University of Debrecen, Debrecen, Hungary.
  • 8 Biosystems International Kft, Debrecen, Hungary.
  • 9 Department of Urology, Medical University of Vienna, Vienna, Austria.
  • 10 Department of Urology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
  • 11 Department of Urology, Semmelweis University, Budapest, Hungary. [email protected].
  • 12 Department of Urology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany. [email protected].
  • # Contributed equally.
PMID: 37634036 DOI: 10.1038/s41391-023-00713-y
Abstract

Background: Abiraterone (Abi) is an Androgen Receptor signaling inhibitor that significantly improves patients' life expectancy in metastatic prostate Cancer (PCa). Despite its beneficial effects, many patients have baseline or acquired resistance against Abi. The aim of this study was to identify predictive serum biomarkers for Abi treatment.

Methods: We performed a comparative proteome analysis on three Abi sensitive (LNCaPabl, LAPC4, DuCaP) and resistant (LNCaPabl-Abi, LAPC4-Abi, DuCaP-Abi) PCa cell lines using liquid chromatography tandem mass spectrometry (LC-MS/MS) technique. Two bioinformatic selection workflows were applied to select the most promising candidate serum markers. Serum levels of selected proteins were assessed in samples of 100 Abi-treated patients with metastatic castration-resistant disease (mCRPC) using ELISA. Moreover, FSCN1 serum concentrations were measured in samples of 69 Docetaxel (Doc) treated mCRPC patients.

Results: Our proteome analysis identified 68 significantly, at least two-fold upregulated proteins in Abi resistant cells. Using two filtering workflows four proteins (AMACR, KLK2, FSCN1 and CTAG1A) were selected for ELISA analyses. We found high baseline FSCN1 serum levels to be significantly associated with poor survival in Abi-treated mCRPC patients. Moreover, the multivariable analysis revealed that higher ECOG status (>1) and high baseline FSCN1 serum levels (>10.22 ng/ml by ROC cut-off) were independently associated with worse survival in Abi-treated patients (p < 0.001 and p = 0.021, respectively). In contrast, no association was found between serum FSCN1 concentrations and overall survival in Doc-treated patients.

Conclusions: Our analysis identified baseline FSCN1 serum levels to be independently associated with poor survival of Abi-treated, but not Doc-treated mCRPC patients, suggesting a therapy specific prognostic value for FSCN1.

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