Abstract 6: Metabolomics of Gleason score in prostate tumor tissue and serum

Abstract

Abstract Background: Gleason score is currently the best clinical predictor of prostate cancer specific-mortality. Identifying biomarkers associated with Gleason score can improve prediction and advance the understanding of the biology of aggressive disease. Using gene expression data, we previously determined that metabolism pathways, including pyrimidine, propanoate, and beta-alanine, were differentially expressed in high and low grade tumors. The goal of this study is to identify metabolites that differ in low and high Gleason score tumors and in blood from these patients. Methods: Metabolic profiling was performed on Gleason score 6 (n = 53) and Gleason score ≥8 (n = 32) radical prostatectomy tumor tissue specimens, and on serum samples from the time of diagnosis (n = 30 Gleason score 6 and n = 19 Gleason score ≥8) from the DF/HCC Prostate Cancer SPORE Cohort. Samples were prepared for analysis by Metabolon, Inc. with their standard solvent extraction method to recover small molecules. Metabolites were identified and quantified by gas and liquid chromatography and mass spectrometry. Missing values were calculated using k-nearest neighbor imputation, and sample values were normalized across batches. The metabolite levels were compared across Gleason score 6 and Gleason score ≥8 tumors and serum using a Wilcoxon test. Results: In the tumor tissue, 207 metabolites were identified. Of these, 30 were present in significantly different amounts in high and low Gleason score tumors, including previously reported citrate (p = 0.002) and spermine (p = 0.003). In a pathway analysis, the propanoate pathway was significantly different in high and low Gleason (p = 0.03), but not the pyrimidine or beta-alanine pathways (p>0.05). In serum, 15 individual metabolites had significantly different levels, including uridine (p = 0.008) and N-acetylserine (p = 0.0001). Conclusions: Metabolite levels do differ in high and low Gleason score prostate tumor tissue. The novel serum results suggest that metabolites in blood may serve as biomarkers of tumor differentiation. Our ongoing research will build prediction models, and will determine if the blood metabolites can indicate the presence of high-Gleason score tumor not detected at biopsy and could serve as biomarkers for monitoring disease progression in active surveillance patients. Citation Format: Kathryn Penney, Svitlana Tyekucheva, Massimo Loda. Metabolomics of Gleason score in prostate tumor tissue and serum. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 6.