(Open access funding provided by Semmelweis University)
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.
