Glutamine and Cholesterol Plasma Levels and Clinical Outcomes of Patients with Metastatic Castration-Resistant Prostate Cancer Treated with Taxanes

SIMPLE SUMMARY: Prostate cancer (PC) is a hormone-dependent disease in which metabolism deregulation has been identified as a relevant event. In particular, glutamine metabolism becomes crucial for biomass and energy production in PC cells. The main aim of this study was to determine whether the plasma glutamine levels correlated with clinical outcomes in patients with metastatic castration resistance prostate cancer (mCRPC) receiving taxanes treatment. We retrospectively assessed the glutamine levels in plasma samples from 75 patients. As glutamine is a precursor of cholesterol production, we also assessed the cholesterol levels in the same cohort, plus 41 extra patients. We found that high glutamine plasma levels were associated with a shorter taxanes response and worse clinical outcome in patients with mCRPC. High cholesterol levels were also indicative of early progression. These results point out circulating glutamine and cholesterol levels as potentially prognostic biomarkers to be further explored in PC. ABSTRACT: Altered metabolism is a hallmark of cancer. Malignant cells metabolise glutamine to fulfil their metabolic needs. In prostate cancer, androgen receptor signalling promotes glutamine metabolism, which is also involved in cholesterol homeostasis. We aimed to determine whether the plasma glutamine levels correlate with the blood lipid profile, clinical characteristics and outcomes in patients with metastatic castration resistance prostate cancer (mCRPC) undergoing taxanes. We retrospectively assessed the glutamine and glutamate levels in plasma samples by a bioluminescent assay. Pre-treatment glutamine, glutamate, cholesterol and triglycerides levels were correlated with patients’ clinical characteristics, taxanes response and clinical outcomes. Seventy-five patients with mCRPC treated with taxanes were included. The plasma glutamine levels were significantly higher in patients that received abiraterone or enzalutamide prior to taxanes (p = 0.003). Besides, patients with low glutamine levels were more likely to present a PSA response to taxanes (p = 0.048). Higher glutamine levels were significantly correlated with shorter biochemical/clinical progression-free survival (PSA/RX-PFS) (median 2.5 vs. 4.2 months; p = 0.048) and overall survival (OS) (median 12.6 vs. 20.3; p = 0.008). High cholesterol levels independently predicted early PSA/RX-PFS (p = 0.034). High glutamine and cholesterol in the plasma from patients with mCRPC were associated with adverse clinical outcomes, supporting the relevance of further research on metabolism in prostate cancer progression.