Metabolites from blood and formalin-fixed, paraffin-embedded tissue from participants with low- and high-grade prostate cancer: a pilot study

Background Identifying metabolites associated with prostate cancer (Pca) aggressiveness may elucidate mechanisms underlying disease severity. Doing so in plasma and formalin-fixed, paraffin-embedded (FFPE) tissue may accelerate discovery. In this cross-sectional pilot study, we generated hypotheses for further exploration by assessing the association between plasma metabolites and the Gleason score of individuals with Pca and by evaluating the correlation between plasma and FFPE metabolite levels. Methods We examined plasma and FFPE samples from 10 individuals with Gleason score 7 (6 3 + 4, 4 4 + 3) and 9 individuals with Gleason score 9 (6 4 + 5, 3 5 + 4) tumors from a convenience sample of 19 men with Pca. We measured the relative abundance of polar metabolites at the time of radical prostatectomy. We used linear models of log 2 fold changes to examine plasma metabolite levels relative to pathological tumor grade. Relationships among metabolite levels measured in plasma and FFPE tumor tissue within individuals across metabolites were examined using Pearson correlations. Results Among the 18 selected plasma metabolites, which were chosen a priori because of their prior association with Pca aggressiveness, serine ( p = 0.0051) and ornithine ( p = 0.036) levels were higher in individuals with Gleason 9 than Gleason 7 Pca. After multiple testing correction, however, no associations were statistically significant. The median correlation between metabolite levels in plasma and FFPE tumor tissue was 0.45 (range: 0.40–0.53) for the 94 metabolites measured in both biospecimens. Conclusions Plasma serine and ornithine levels demonstrated the largest differences between individuals with Gleason 7 and Gleason 9 Pca. Metabolite levels in FFPE prostate tissue samples were moderately correlated with plasma levels. Future studies with larger sample sizes are needed to further explore the hypotheses generated by this study.