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Prognostic implication of blood immune cell composition in Metastatic Castration-Resistant Prostate Cancer (mCRPC)

ABSTRACT: The prognosis of patients with metastatic castration-resistant prostate cancer (mCRPC) is variable. Several blood-related prognostic factors have been reported, including transcriptional profiling of whole blood and neutrophil to lymphocyte ratio. We aimed to address the contribution of distinct whole blood immune cell components to the prognosis of these patients. Subjects/Patients and Methods: Pre-treatment whole blood samples from chemotherapy-naïve mCRPC patients were prospectively collected before treatment with enzalutamide. The study consisted of a training cohort including 98 patients treated with enzalutamide in a phase 2 biomarker clinical trial (NCT02288936)

ORGANISM(S): Homo sapiens

PROVIDER: GSE248619 | GEO | 2024/08/02

REPOSITORIES: GEO

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Project description: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. Objective: To identify predictive serum biomarkers for Abi treatment. Design, setting, and participants: 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 methods 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 using ELISA. Moreover, FSCN1 serum concentrations were measured in samples of 69 Docetaxel (Doc) treated mCRPC patients. Outcome measurements and statistical analysis: Serum levels were correlated with patients‘ clinicopathological parameters and survival. Results and limitations: Our proteome analysis identified 68 significantly, at least two-fold upregulated proteins in Abi resistant cells. Using two filtering methods 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. Patient summary: In this study, we identified serum FSCN1 as a marker that may help to predict PCa patients who derive less benefit from Abi but not Doc treatment.

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Prognostic implication of blood immune cell composition in Metastatic Castration-Resistant Prostate Cancer (mCRPC)

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