Department of Urology, Semmelweis University, Budapest, Hungary.
Department of Molecular Biology, Semmelweis University, Budapest, Hungary.
Prostate Cancer Prostatic Dis. 2024 Sep;27(3):451-456. doi: 10.1038/s41391-023-00713-y. Epub 2023 Aug 26.
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.
阿比特龙（Abi）是一种雄激素受体信号抑制剂，可显著提高转移性前列腺癌（PCa）患者的预期寿命。尽管它有有益的效果，但许多患者对 Abi 具有基线或获得性耐药性。本研究旨在确定 Abi 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 Abi 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。应用两种生物信息学选择工作流程来选择最有前途的候选血清标志物。使用 ELISA 评估了 100 名接受转移性去势抵抗性疾病（mCRPC）Abi 治疗的患者的血清样本中选定蛋白的水平。此外，还在 69 名接受多西紫杉醇（Doc）治疗的 mCRPC 患者的样本中测量了 FSCN1 血清浓度。
我们的蛋白质组分析确定了 Abi 耐药细胞中至少有 68 种显著上调的蛋白质。使用两种过滤工作流程，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 Abi 治疗的 mCRPC 患者的不良生存显著相关。此外，多变量分析显示，ECOG 状态较高（>1）和高基线 FSCN1 血清水平（通过 ROC 截断值>10.22ng/ml）与 Abi 治疗患者的生存恶化独立相关（p<0.001 和 p=0.021）。相比之下，在接受 Doc 治疗的患者中，血清 FSCN1 浓度与总生存无相关性。
我们的分析确定基线 FSCN1 血清水平与 Abi 治疗但不是 Doc 治疗的 mCRPC 患者的不良生存独立相关，这表明 FSCN1 具有治疗特异性的预后价值。
