Metabolomics of Prostate Cancer Gleason Score in Tumor Tissue and Serum.

TitleMetabolomics of Prostate Cancer Gleason Score in Tumor Tissue and Serum.
Publication TypeJournal Article
Year of Publication2021
AuthorsPenney KL, Tyekucheva S, Rosenthal J, Fandy HEl, Carelli R, Borgstein S, Zadra G, Fanelli GNicol├▓, Stefanizzi L, Giunchi F, Pomerantz M, Peisch S, Coulson H, Lis R, Kibel AS, Fiorentino M, Umeton R, Loda M
JournalMol Cancer Res
Volume19
Issue3
Pagination475-484
Date Published2021 03
ISSN1557-3125
Abstract

Gleason score, a measure of prostate tumor differentiation, is the strongest predictor of lethal prostate cancer at the time of diagnosis. Metabolomic profiling of tumor and of patient serum could identify biomarkers of aggressive disease and lead to the development of a less-invasive assay to perform active surveillance monitoring. Metabolomic profiling of prostate tissue and serum samples was performed. Metabolite levels and metabolite sets were compared across Gleason scores. Machine learning algorithms were trained and tuned to predict transformation or differentiation status from metabolite data. A total of 135 metabolites were significantly different ( < 0.05) in tumor versus normal tissue, and pathway analysis identified one sugar metabolism pathway ( = 0.03). Machine learning identified profiles that predicted tumor versus normal tissue (AUC of 0.82 ┬▒ 0.08). In tumor tissue, 25 metabolites were associated with Gleason score (unadjusted < 0.05), 4 increased in high grade while the remainder were enriched in low grade. While pyroglutamine and 1,5-anhydroglucitol were correlated (0.73 and 0.72, respectively) between tissue and serum from the same patient, no metabolites were consistently associated with Gleason score in serum. Previously reported as well as novel metabolites with differing abundance were identified across tumor tissue. However, a "metabolite signature" for Gleason score was not obtained. This may be due to study design and analytic challenges that future studies should consider. IMPLICATIONS: Metabolic profiling can distinguish benign and neoplastic tissues. A novel unsupervised machine learning method can be utilized to achieve this distinction.

DOI10.1158/1541-7786.MCR-20-0548
Alternate JournalMol Cancer Res
PubMed ID33168599
PubMed Central IDPMC8369519
Grant ListP50 CA090381 / CA / NCI NIH HHS / United States
P50 CA211024 / CA / NCI NIH HHS / United States
R01 CA131945 / CA / NCI NIH HHS / United States
Related Faculty: 
Massimo Loda, M.D.

Pathology & Laboratory Medicine 1300 York Avenue New York, NY 10065 Phone: (212) 746-6464
Surgical Pathology: (212) 746-2700