Abstract
BACKGROUND: Prostate cancer (PCa) is the second most prevalent cancer in males worldwide, yet detecting PCa and its metastases remains a major challenging task in clinical research setups. The present study aimed to characterize the metabolic changes underlying the PCa progression and investigate the efficacy of related metabolic panels for an accurate PCa assessment. METHODS: In the present study, 75 PCa subjects, 62 PCa patients with bone metastasis (PCaB), and 50 benign prostatic hyperplasia (BPH) patients were enrolled, and we performed a cross-sectional metabolomics analysis of serum samples collected from these subjects using a (1)H nuclear magnetic resonance (NMR)-based metabolomics approach. RESULTS: Multivariate analysis revealed that BPH, PCa, and PCaB groups showed distinct metabolic divisions, while univariate statistics integrated with variable importance in the projection (VIP) scores identified a differential metabolite series, which included energy, amino acid, and ketone body metabolism. Herein, we identified a series of characteristic serum metabolic changes, including decreased trends of 3-HB and acetone as well as elevated trends of alanine in PCa patients compared with BPH subjects, while increased levels of 3-HB and acetone as well as decreased levels of alanine in PCaB patients compared with PCa. Additionally, our results also revealed the metabolic panels of discriminant metabolites coupled with the clinical parameters (age and body mass index) for discrimination between PCa and BPH, PCaB and BPH, PCaB and PCa achieved the AUC values of 0.828, 0.917, and 0.872, respectively. CONCLUSIONS: Overall, our study gave successful discrimination of BPH, PCa and PCaB, and we characterized the potential metabolic alterations involved in the PCa progression and its metastases, including 3-HB, acetone and alanine. The defined biomarker panels could be employed to aid in the diagnosis and classification of PCa in clinical practice.