title: Diagnostic Metabolomic Blood Tests for Endoluminal Gastrointestinal Cancer--A Systematic Review and Assessment of Quality.
abstract: Advances in analytics have resulted in metabolomic blood tests being developed for the detection of cancer. This systematic review aims to assess the diagnostic accuracy of blood-based metabolomic biomarkers for endoluminal gastrointestinal (GI) cancer. Using endoscopic diagnosis as a reference standard, methodologic and reporting quality was assessed using validated tools, in addition to pathway-based informatics to biologically contextualize discriminant features. Twenty-nine studies (15 colorectal, 9 esophageal, 3 gastric, and 2 mixed) with data from 10,835 participants were included. All reported significant differences in hematologic metabolites. In pooled analysis, 246 metabolites were found to be significantly different after multiplicity correction. Incremental metabolic flux with disease progression was frequently reported. Two promising candidates have been validated in independent populations (both colorectal biomarkers), and one has been approved for clinical use. Networks analysis suggested modulation of elements of up to half of Edinburgh Human Metabolic Network subdivisions, and that the poor clinical applicability of commonly modulated metabolites could be due to extensive molecular interconnectivity. Methodologic and reporting quality was assessed as moderate-to-poor. Serum metabolomics holds promise for GI cancer diagnostics; however, future efforts must adhere to consensus standardization initiatives, utilize high-resolution discovery analytics, and compare candidate biomarkers with peer nonendoscopic alternatives.
authors.affiliation: Division of Surgery, Department of Surgery and Cancer, Imperial College London, London, United Kingdom.
authors.forename: Stefan
authors.initials: S
authors.lastname: Antonowicz
authors.affiliation: Division of Surgery, Department of Surgery and Cancer, Imperial College London, London, United Kingdom.
authors.forename: Sacheen
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Division of Surgery, Department of Surgery and Cancer, Imperial College London, London, United Kingdom.
authors.forename: Tom
authors.initials: T
authors.lastname: Wiggins
authors.affiliation: Division of Surgery, Department of Surgery and Cancer, Imperial College London, London, United Kingdom.
authors.forename: Sheraz R
authors.initials: SR
authors.lastname: Markar
authors.affiliation: Division of Surgery, Department of Surgery and Cancer, Imperial College London, London, United Kingdom. g.hanna@imperial.ac.uk.
authors.forename: George B
authors.initials: GB
authors.lastname: Hanna
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood*; D018450:Disease Progression; D005770:Gastrointestinal Neoplasms / Q000175:diagnosis* / Q000378:metabolism*; D006403:Hematologic Tests / Q000379:methods*; D006801:Humans; D055432:Metabolomics / Q000379:methods*; D011379:Prognosis
chemical_list: D015415:Biomarkers