Meta‐analysis of clinical metabolic profiling studies in cancer: challenges and opportunities

• Published in: EMBO molecular medicine 2016-10, Vol.8 (10), p.1134-1142
• Main Authors: Goveia, Jermaine, Pircher, Andreas, Conradi, Lena‐Christin, Kalucka, Joanna, Lagani, Vincenzo, Dewerchin, Mieke, Eelen, Guy, DeBerardinis, Ralph J, Wilson, Ian D, Carmeliet, Peter
• Format: Article
• Language: English
• Subjects: Biomarkers; Cancer; Data mining; Datasets; Diabetes; Disease; EMBO03; EMBO21; EMBO42; Genomics; Glycolysis; Grants; Histidine; Humans; Identification; Ketones; Meta-analysis; metabolic profiling; Metabolism; Metabolites; Metabolome; Metabolomics; Metabolomics - methods; Metabolomics - standards; Neoplasms - pathology; Pathogenesis; Proteomics; Retrospective Studies; Standardization; Studies; Tryptophan; Urine
• ISSN: 1757-4676; 1757-4684
• DOI: 10.15252/emmm.201606798

Cancer cell metabolism has received increasing attention. Despite a boost in the application of clinical metabolic profiling (CMP) in cancer patients, a meta‐analysis has not been performed. The primary goal of this study was to assess whether public accessibility of metabolomics data and identification and reporting of metabolites were sufficient to assess which metabolites were consistently altered in cancer patients. We therefore retrospectively curated data from CMP studies in cancer patients published during 5 recent years and used an established vote‐counting method to perform a semiquantitative meta‐analysis of metabolites in tumor tissue and blood. This analysis confirmed well‐known increases in glycolytic metabolites, but also unveiled unprecedented changes in other metabolites such as ketone bodies and amino acids (histidine, tryptophan). However, this study also highlighted that insufficient public accessibility of metabolomics data, and inadequate metabolite identification and reporting hamper the discovery potential of meta‐analyses of CMP studies, calling for improved standardization of metabolomics studies. Synopsis The results of clinical metabolic profiling studies in cancer were curated and a meta‐analysis was subsequently performed to identify deregulated metabolites in blood, tissue, and urine. Metabolic alterations in glucose and glutamine metabolism were identified, as well as changes in 3‐hydroxybutyrate, histidine, and tryptophan levels, previously less associated with cancer. While a meta‐analysis of metabolic profiling is potentially powerful, it is currently limited by the incomplete (meta)data reporting and the lack of publicly available data. The use of recently established metabolomics databases and the deposition of full datasets in public repositories could significantly improve the impact of clinical metabolic profiling. Graphical Abstract The results of clinical metabolic profiling studies in cancer were curated and a meta‐analysis was subsequently performed to identify deregulated metabolites in blood, tissue, and urine.