title: Metabolomics and transcriptomics identify pathway differences between visceral and subcutaneous adipose tissue in colorectal cancer patients: the ColoCare study.
abstract: BACKGROUND
  Metabolic and transcriptomic differences between visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) compartments, particularly in the context of obesity, may play a role in colorectal carcinogenesis. We investigated the differential functions of their metabolic compositions.
  
  
  OBJECTIVE
  Biochemical differences between adipose tissues (VAT compared with SAT) in patients with colorectal carcinoma (CRC) were investigated by using mass spectrometry metabolomics and gene expression profiling. Metabolite compositions were compared between VAT, SAT, and serum metabolites. The relation between patients' tumor stage and metabolic profiles was assessed.
  
  
  METHODS
  Presurgery blood and paired VAT and SAT samples during tumor surgery were obtained from 59 CRC patients (tumor stages I-IV) of the ColoCare cohort. Gas chromatography time-of-flight mass spectrometry and liquid chromatography quadrupole time-of-flight mass spectrometry were used to measure 1065 metabolites in adipose tissue (333 identified compounds) and 1810 metabolites in serum (467 identified compounds). Adipose tissue gene expression was measured by using Illumina's HumanHT-12 Expression BeadChips.
  
  
  RESULTS
  Compared with SAT, VAT displayed elevated markers of inflammatory lipid metabolism, free arachidonic acid, phospholipases (PLA2G10), and prostaglandin synthesis-related enzymes (PTGD/PTGS2S). Plasmalogen concentrations were lower in VAT than in SAT, which was supported by lower gene expression of FAR1, the rate-limiting enzyme for ether-lipid synthesis in VAT. Serum sphingomyelin concentrations were inversely correlated (P = 0.0001) with SAT adipose triglycerides. Logistic regression identified lipids in patients' adipose tissues, which were associated with CRC tumor stage.
  
  
  CONCLUSIONS
  As one of the first studies, we comprehensively assessed differences in metabolic, lipidomic, and transcriptomic profiles between paired human VAT and SAT and their association with CRC tumor stage. We identified markers of inflammation in VAT, which supports prior evidence regarding the role of visceral adiposity and cancer.
authors.affiliation: Division of Preventive Oncology, National Center for Tumor Diseases and German Cancer Research Center, Heidelberg, Germany;
authors.forename: David B
authors.initials: DB
authors.lastname: Liesenfeld
authors.affiliation: NIH West Coast Metabolomics Center and University of California, Davis, CA;
authors.forename: Dmitry
authors.initials: D
authors.lastname: Grapov
authors.affiliation: NIH West Coast Metabolomics Center and University of California, Davis, CA;
authors.forename: Johannes F
authors.initials: JF
authors.lastname: Fahrmann
authors.affiliation: Division of Preventive Oncology, National Center for Tumor Diseases and German Cancer Research Center, Heidelberg, Germany;
authors.forename: Mariam
authors.initials: M
authors.lastname: Salou
authors.affiliation: Division of Preventive Oncology, National Center for Tumor Diseases and German Cancer Research Center, Heidelberg, Germany;
authors.forename: Dominique
authors.initials: D
authors.lastname: Scherer
authors.affiliation: Division of Preventive Oncology, National Center for Tumor Diseases and German Cancer Research Center, Heidelberg, Germany;
authors.forename: Reka
authors.initials: R
authors.lastname: Toth
authors.affiliation: Division of Preventive Oncology, National Center for Tumor Diseases and German Cancer Research Center, Heidelberg, Germany;
authors.forename: Nina
authors.initials: N
authors.lastname: Habermann
authors.affiliation: Division of Preventive Oncology, National Center for Tumor Diseases and German Cancer Research Center, Heidelberg, Germany;
authors.forename: Jürgen
authors.initials: J
authors.lastname: Böhm
authors.affiliation: Division of Preventive Oncology, National Center for Tumor Diseases and German Cancer Research Center, Heidelberg, Germany;
authors.forename: Petra
authors.initials: P
authors.lastname: Schrotz-King
authors.affiliation: Division of Preventive Oncology, National Center for Tumor Diseases and German Cancer Research Center, Heidelberg, Germany;
authors.forename: Biljana
authors.initials: B
authors.lastname: Gigic
authors.affiliation: Department of General and Transplantation Surgery, University of Heidelberg, Germany;
authors.forename: Martin
authors.initials: M
authors.lastname: Schneider
authors.affiliation: Department of General and Transplantation Surgery, University of Heidelberg, Germany;
authors.forename: Alexis
authors.initials: A
authors.lastname: Ulrich
authors.affiliation: Tissue Bank of the National Center for Tumor Diseases, Heidelberg, Germany; Institute of Pathology, University Hospital Heidelberg, Germany;
authors.forename: Esther
authors.initials: E
authors.lastname: Herpel
authors.affiliation: Institute of Pathology, University Hospital Heidelberg, Germany;
authors.forename: Peter
authors.initials: P
authors.lastname: Schirmacher
authors.affiliation: NIH West Coast Metabolomics Center and University of California, Davis, CA;
authors.forename: Oliver
authors.initials: O
authors.lastname: Fiehn
authors.affiliation: Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, WA; and.
authors.forename: Johanna W
authors.initials: JW
authors.lastname: Lampe
authors.affiliation: Division of Preventive Oncology, National Center for Tumor Diseases and German Cancer Research Center, Heidelberg, Germany; Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, WA; and Population Sciences, Huntsman Cancer Institute, Salt Lake City, UT neli.ulrich@hci.utah.edu.
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: Ulrich
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology* / Q000601:surgery; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology* / Q000601:surgery; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D050152:Intra-Abdominal Fat / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D050356:Lipid Metabolism; D008297:Male; D055432:Metabolomics / Q000379:methods; D008875:Middle Aged; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D015434:Panniculitis / Q000209:etiology* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D010257:Paraneoplastic Syndromes / Q000209:etiology* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D011446:Prospective Studies; D050507:Subcutaneous Fat, Abdominal / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
chemical_list: D015415:Biomarkers
keywords: adipose tissue; colorectal cancer; inflammation; metabolomics; obesity; visceral adiposity