O241: A multi-omic systematic review of metabolites involved in predicting of the response to neoadjuvant therapy in locally advanced rectal cancer

Abstract

Abstract Introduction Locally advanced rectal cancer (LARC), treated with neoadjuvant chemoradiotherapy (NCRT), displays varying treatment responses. Despite extensive research in the "omics" fields, clinical practice lacks NCRT predictive biomarkers for LARC. Metabolomics, an emerging "omics" discipline, quantitatively assesses small metabolites' influence on the phenotype and has successfully identified biomarkers for cancer diagnosis, therapy, and prognosis, including colorectal cancer. Therefore, this systematic review aimed to identify metabolomic studies in LARC patients undergoing NCRT and elucidate treatment response-associated metabolic pathways. Methods A systematic review was performed using Pubmed, Web of Science, and Scopus, collating statistically significant metabolites from selected studies. Subsequently, pathway and enrichment analyses were performed using Metaboanalyst 5.0. Results Eight eligible studies examined 184 metabolites. Pathway analysis revealed fifteen significant metabolic pathways, notably emphasizing alanine and branched chain amino acid metabolism. Enrichment analysis confirmed the importance of alanine metabolism, alongside oxidative phosphorylation, gluconeogenesis, and glycolysis. Discussion In these pathways, paramount significance lies in their ability to generate ATP to meet increased energy demands via oxidative phosphorylation and gluconeogenesis, crucial in the context of NCRT. Furthermore, pathways proficient in neutralizing harmful reactive oxidation species, contributors to radiation-induced DNA damage, play a critical role in treatment response determination. In summary, the metabolomic landscape in LARC patients undergoing NCRT sheds light on pivotal pathways for predicting treatment response. These findings underscore the importance of energy metabolism and the attenuation of oxidative stress as promising avenues for further research and the development of LARC therapy predictive biomarkers.