阿比特隆（Abi）是一种抗雄激素受体信号抑制剂，可以显著提高转移性前列腺癌（PCa）患者的寿命。尽管具有益处，许多患者对阿比特隆具有基线或获得性耐药性。本研究的目的是鉴定阿比特隆治疗的预测性血清生物标志物。我们使用液相色谱串联质谱（LC-MS/MS）技术对三种可敏感（LNCaPabl，LAPC4，DuCaP）和耐药（LNCaPabl-Abi，LAPC4-Abi，DuCaP-Abi）的PCa细胞系进行了比较蛋白质组分析。我们应用了两种生物信息学筛选流程，选择了最有希望的候选血清标记物。选择的蛋白质的血清水平在100例转移性去势抵抗性疾病（mCRPC）的Abi治疗患者样本中通过ELISA进行评估。此外，还在69例多西他赛（Doc）治疗的mCRPC患者样本中测量了FSCN1的血清浓度。我们的蛋白质组分析确定了阿比特隆耐药细胞中68种显著上调至少两倍的蛋白质。通过两个筛选流程，我们选择了四种蛋白质（AMACR，KLK2，FSCN1和CTAG1A）进行ELISA分析。我们发现高基线FSCN1血清水平与接受Abi治疗的mCRPC患者的预后差相关。此外，多变量分析发现较高的ECOG状态（>1）和高基线FSCN1血清水平（>10.22 ng/ml 根据ROC截断）与接受Abi治疗患者的更差预后独立相关（p < 0.001和p = 0.021）。相反，血清FSCN1浓度与多西他赛治疗患者的总生存率无关。我们的分析发现，基线FSCN1血清水平与接受阿比特隆治疗的mCRPC患者的不良预后独立相关，但与多西他赛治疗的mCRPC患者的总体生存率无关，提示FSCN1在治疗特异性预后价值。© 2023. 作者。

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.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.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.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.© 2023. The Author(s).