Altered amino and fatty acids metabolism in Sudanese prostate cancer patients: insights from metabolic analysis

Abstract

Introduction: Prostate cancer (PCa) management presents a multifaceted clinical challenge, intricately linking oncological considerations with cardiovascular health. Despite the recognized importance of lipid metabolism and hypertension in this interwoven relationship, their involvement in PCa development remains partially understood. This study aimed to explore variations in plasma metabolome among Sudanese PCa patients and their associated comorbidities.

Methods: Plasma samples were collected from 50 patients across four hospitals in Sudan and profiled by nuclear magnetic resonance (NMR) spectroscopy. One-dimensional proton NMR spectra were acquired for each sample using standard nuclear Overhauser effect spectroscopy pulse sequence presat on a 500 MHz Bruker Avance III HD NMR spectrometer. Metabolite concentrations were quantified using R scripts developed in-house. Univariate and multivariate analyses were generated in the R software.

Results: Patients were categorized into four distinct metabotypes based on their metabolic profiles, and statistical analyses were conducted to evaluate the significance of observed differences. Our findings revealed high levels of fatty acids, phospholipids, cholesterol, valine, leucine, and isoleucine associated with non-hypertensive patients. In contrast, hypertensive patients were associated with high GlycA and GlycB levels and altered amino acid metabolism.

Conclusion: These findings underscore the intricate interplay between metabolic dysregulation and hypertension in PCa patients. Further research is warranted to elucidate the precise molecular pathways underlying lipid metabolism in PCa and to explore the therapeutic potential of targeting these pathways. In conclusion, our study contributes to a deeper understanding of the metabolic landscape of PCa in Sudanese patients, emphasizing the importance of personalized approaches in cancer management.

Keywords: Africa; Metabolomics; NMR; Prostate cancer; Sudan.

FIGURE 1 -

Descriptive analysis for NMR metabolic profile of PCa patients. A) Correlation matrix of Spearman’s rank correlation coefficients between the estimated metabolites. B) KODAMA plot visualizing four metabotypes. C) Heatmap showing the comparison of immune cell profiles across four metabotypes. HTN = hypertension; NMR = nuclear magnetic resonance; PCa = prostate cancer.

FIGURE 2 -

Variations in significant metabolites across four predicted metabotypes. A) Balloon plot representing the different metabolite concentrations across the four metabotypes. The KODAMA plots illustrate the distribution of cholesterol (B) and GlycB concentrations (C), with concentrations represented by varying point sizes across four distinct metabotypes. HTN = hypertension.

FIGURE 3 -

Association between hypertension (HTN) and metabolite concentrations. Odds ratio for HTN per 1-standard deviation increment in metabolite concentration with 95% confidence interval (CI). The red circle represents significant values.