Metabolomics of Prostate Cancer Gleason Score in Tumor Tissue and Serum
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 (Padjusted < 0.05) in tumor versus normal tissue, and pathway analysis identified one sugar metabolism pathway (Padjusted = 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 P < 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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Mar 01, 2021
- Source ID
- 10.1158/1541-7786.mcr-20-0548
Entities
People
- Adam S. Kibel
- Francesca Giunchi
- Giorgia Zadra
- Giuseppe Nicolò Fanelli
- Habiba El Fandy
- Hannah Coulson
- Jacob Rosenthal
- Kathryn L. Penney
- Lavinia Stefanizzi
- Mark Pomerantz
- Massimo Loda
- Michelangelo Fiorentino
- Renato Umeton
- Rosina T Lis
- Ryan Carelli
- Samuel Peisch
- Stephanie Borgstein
- Svitlana Tyekucheva
Organizations
- Brigham and Women's Hospital
- Cairo University
- Dana–Farber Cancer Institute
- Harvard Medical School
- Harvard University
- National Institutes of Health
- United States Department of Defense
- University of Bologna
- University of Pisa
- Weill Cornell Medicine