Objective:Upper gastrointestinal (UGI) cancers,predominantly gastric cancer (GC) and esophageal cancer (EC),are malignant tumor types with high morbidity and mortality rates.Accumulating studies have focused on metabolomic profiling of UGI cancers in recent years.In this systematic review,we have provided a collective summary of previous findings on metabolites and metabolomic profiling associated with GC and EC.Methods:A systematic search of three databases (Embase,PubMed,and Web of Science) for molecular epidemiologic studies on the metabolomic profiles of GC and EC was conducted.The Newcastle-Ottawa Scale (NOS) was used to assess the quality of the included articles.Results:A total of 52 original studies were included for review.A number of metabolites were differentially distributed between GC and EC cases and non-cases,including those involved in glycolysis,anaerobic respiration,tricarboxylic acid cycle,and protein and lipid metabolism.Lactic acid,glucose,citrate,and fumaric acid were among the most frequently reported metabolites of cellular respiration while glutamine,glutamate,and valine were among the most commonly reported amino acids.The lipid metabolites identified previously included saturated and unsaturated free fatty acids,aldehydes,and ketones.However,the key findings across studies to date have been inconsistent,potentially due to limited sample sizes and the majority being hospital-based case-control analyses lacking an independent replication group.Conclusions:Studies on metabolomics have thus far provided insights into etiological factors and biomarkers for UGI cancers,supporting the potential of applying metabolomic profiling in cancer prevention and management efforts.