Unveiling Disrupted Lipid Metabolism in Benign Prostate Hyperplasia, Prostate Cancer, and Metastatic Patients: Insights from a Colombian Nested Case–Control Study

SIMPLE SUMMARY: Prostate cancer represents a substantial global health issue, and its intricacies continue to pose challenges for complete comprehension. In this study, an untargeted metabolomic and lipidomic approach was employed to analyze plasma samples obtained from patients diagnosed with benign prostatic hyperplasia (BPH), prostate cancer (PCa), and metastatic prostate cancer (Met). The results revealed significant changes in lipid metabolism when comparing patients with prostate cancer to those with benign prostatic hyperplasia and patients with metastasis. These findings support the fundamental importance of lipid metabolism in the development and progression of prostate cancer. ABSTRACT: Prostate cancer is a significant global health concern, and its prevalence is increasing worldwide. Despite extensive research efforts, the complexity of the disease remains challenging with respect to fully understanding it. Metabolomics has emerged as a powerful approach to understanding prostate cancer by assessing comprehensive metabolite profiles in biological samples. In this study, metabolic profiles of patients with benign prostatic hyperplasia (BPH), prostate cancer (PCa), and metastatic prostate cancer (Met) were characterized using an untargeted approach that included metabolomics and lipidomics via liquid chromatography and gas chromatography coupled with high-resolution mass spectrometry. Comparative analysis among these groups revealed distinct metabolic profiles, primarily associated with lipid biosynthetic pathways, such as biosynthesis of unsaturated fatty acids, fatty acid degradation and elongation, and sphingolipid and linoleic acid metabolism. PCa patients showed lower levels of amino acids, glycerolipids, glycerophospholipids, sphingolipids, and carnitines compared to BPH patients. Compared to Met patients, PCa patients had reduced metabolites in the glycerolipid, glycerophospholipid, and sphingolipid groups, along with increased amino acids and carbohydrates. These altered metabolic profiles provide insights into the underlying pathways of prostate cancer’s progression, potentially aiding the development of new diagnostic, and therapeutic strategies.