title: Integrative metabolome and transcriptome profiling reveals discordant glycolysis process between osteosarcoma and normal osteoblastic cells.
abstract: BACKGROUND
  Osteosarcoma (OS) is the most common primary malignant tumor of bone in children and adolescents. However, few biomarkers of diagnostic significance have been established. In recent years, high-throughput transcriptomic and metabolomic approaches make it possible for studying the levels of thousands of biomarkers simultaneously.
  
  
  METHODS
  In this study, we integrated two disparate transcriptomic and metabolomic datasets to find meaningful biomarkers and then used an independent dataset to test the sensibility and specificity of these biomarkers.
  
  
  RESULTS
  By using integrated two datasets, we discovered that the biomarkers involved in the glycolysis pathway are highly enriched, including 4 genes (ENO1, TPI1, PKG1 and LDHC) and 2 metabolites (lactate and pyruvate). The 4 genes were significantly down-regulated in OS samples as well as the 2 metabolites. The mixed metabolites + genes signature also outperformed metabolites or genes alone, with recall being 0.813 and F-measure being 0.812. And the AUC value of metabolites + genes classifier was 0.825 (compared to 0.58 for metabolites and 0.821 for genes alone).
  
  
  CONCLUSIONS
  Our findings establish that integrated transcriptomic and metabolomic signature can be used to distinguish OS malignant with good diagnostic accuracy superior to other methods.
authors.affiliation: Department of Orthopaedics, Shanghai Tenth People's Hospital, Tongji University, Shanghai, 200072, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Chen
authors.forename: Chunyan
authors.initials: C
authors.lastname: Zhu
authors.forename: Ming
authors.initials: M
authors.lastname: Cai
authors.forename: Dong
authors.initials: D
authors.lastname: Fu
authors.forename: Biao
authors.initials: B
authors.lastname: Cheng
authors.forename: Zhengdong
authors.initials: Z
authors.lastname: Cai
authors.forename: Guodong
authors.initials: G
authors.lastname: Li
authors.forename: Jilong
authors.initials: J
authors.lastname: Liu
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D016022:Case-Control Studies; D062965:Cyclic GMP-Dependent Protein Kinase Type I / Q000378:metabolism; D015536:Down-Regulation; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005943:Gluconeogenesis / Q000235:genetics; D006019:Glycolysis / Q000235:genetics; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D019344:Lactic Acid / Q000097:blood; D055442:Metabolome; D010006:Osteoblasts / Q000378:metabolism*; D012516:Osteosarcoma / Q000175:diagnosis / Q000378:metabolism*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D011237:Predictive Value of Tests; D019289:Pyruvic Acid / Q000097:blood; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; D019344:Lactic Acid; D019289:Pyruvic Acid; D007770:L-Lactate Dehydrogenase; D062965:Cyclic GMP-Dependent Protein Kinase Type I; D010751:Phosphopyruvate Hydratase