Table 1. Comparison of the loadings from canonical variate analysis (CVA) of all 3 oxygen conditions.
Metabolite | HCT 116: loading common between WT and DN | HEPA-1: loading common between WT and C4 |
---|---|---|
4-aminobutyrate | normoxia | |
4-hydroxyproline | normoxia | |
Allose/Mannose/Galactose /Glucose (1) | * | * |
Allose/Mannose/Galactose /Glucose (2) | * | * |
Allose/Mannose/Galactose /Glucose (3) | normoxia | |
2-hydroxyglutarate | low oxygen | |
2-oxoglutarate | normoxia* | normoxia* |
Aspartate (1) | normoxia | |
Aspartate (2) | normoxia* | normoxia* |
Beta-alanine | normoxia | |
Citrate | normoxia* | normoxia* |
Creatinine | low oxygen | |
Cysteine | normoxia | |
Erythronate /Threonate | low oxygen* | low oxygen* |
Fructose (1) | * | * |
Fructose (2) | normoxia | |
Fructose / Sorbose (1) | low oxygen | |
Fructose / Sorbose (2) | low oxygen* | low oxygen* |
Glutamate | normoxia | low oxygen |
Glutamine | normoxia* | normoxia* |
Glycerol | low oxygen* | low oxygen* |
Glycerol-3-phosphate | low oxygen | |
Glycine | low oxygen | |
Hexadecanoic acid | * | * |
Hypotaurine | low oxygen* | low oxygen* |
Lactate | low oxygen* | low oxygen* |
Leucine | N/A | |
Lysine | low oxygen | |
Malate | normoxia | |
Malonate | low oxygen* | low oxygen* |
Methionine | low oxygen* | low oxygen* |
Norleucine | low oxygen* | low oxygen* |
Phosphate | low oxygen* | low oxygen* |
Phosphocreatinine | N/A | |
Putrescine | normoxia* | normoxia* |
Pyroglutamate | normoxia | |
Pyruvate | normoxia | |
Scyllo-/Myo-inositol | * | * |
Octadecenoic acid | * | * |
Threonine | low oxygen* | low oxygen* |
Tyramine/Tyrosine | low oxygen | |
Tyrosine | normoxia* | normoxia* |
xylitol/Ribitol | low oxygen | N/A |
CVA was performed for HCT 116 wild type (WT) samples, HCT 116 dominant negative (DN) samples HEPA-1 WT samples and HEPA-1 C4 samples (Fig. 3a–d). Metabolites labelled ‘normoxia’ were identified in the loadings as being features of normoxia that were common between WT and HIF-1 deficient cells, while metabolites labelled ‘low oxygen’ were identified in the loadings as being features of low oxygen that were common between WT and hypoxia inducible factor 1 (HIF-1) deficient cells. Un-labelled metabolites represent HIF-1 mediated responses to oxygen since the loadings were not common between WT and HIF-1 deficient cells. Metabolites marked with an asterisk (*) indicate cell line similarities such that the same behaviour was observed in both HCT 116 and HEPA-1cell lines.