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

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.

Assessing Metabolic Risk Factors for LVSI in Endometrial Cancer: A Cross-Sectional Study

“…32 On the other hand, lipid metabolism played an important role in the LVSI of type 2 EC, mainly consisting of nonendometrioid adenocarcinoma. Many studies have shown that cholesterol is closely related to the metastasis of hormone-dependent tumors, such as prostate cancer, 33 breast cancer, 34 and EC. 35 In addition, Kho et al performed a bidirectional, two-sample Mendelian randomization analysis to investigate the relationship between levels of three blood lipids and EC risk in a large population.…”

Osteoclasts directly influence castration-resistant prostate cancer cells

“…Cholesterol is a vital component in cell membranes and a precursor for steroid synthesis, including androgens. In prostate cancer, high cholesterol and cholesterol biosynthesis have been associated with for example progression [ 48 ], metastasis [ 49 ], and poor treatment response to taxanes [ 50 ]. Together with the downregulation of the cholesterol synthesis pathway by ostecoclasts in the present study, this would indicate a suppressive role of osteoclasts on aggressive features associated with cholesterol.…”

Hormone-Glutamine Metabolism: A Critical Regulatory Axis in Endocrine-Related Cancers

“…It has been reported that the LNCaP cell, an androgen-sensitive line of prostate cancer cells, can directly utilize glutamine for fatty acid production, and so glutamine was identified as a precursor of fatty acids and cholesterol in PC cells [ 48 ], which has been confirmed by subsequent studies [ 50 , 51 ]. This pathway may be due to a process referred to as reductive carboxylation.…”