David B Liesenfeld1, Dmitry Grapov2, Johannes F Fahrmann2, Mariam Salou1, Dominique Scherer1, Reka Toth1, Nina Habermann1, Jürgen Böhm1, Petra Schrotz-King1, Biljana Gigic1, Martin Schneider3, Alexis Ulrich3, Esther Herpel4, Peter Schirmacher5, Oliver Fiehn2, Johanna W Lampe6, Cornelia M Ulrich7. 1. Division of Preventive Oncology, National Center for Tumor Diseases and German Cancer Research Center, Heidelberg, Germany; 2. NIH West Coast Metabolomics Center and University of California, Davis, CA; 3. Department of General and Transplantation Surgery, University of Heidelberg, Germany; 4. Tissue Bank of the National Center for Tumor Diseases, Heidelberg, Germany; Institute of Pathology, University Hospital Heidelberg, Germany; 5. Institute of Pathology, University Hospital Heidelberg, Germany; 6. Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, WA; and. 7. 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.
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. OBJECTIVES: 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. DESIGN: 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.
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. OBJECTIVES: 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. DESIGN: Presurgery blood and paired VAT and SAT samples during tumor surgery were obtained from 59 CRCpatients (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: David B Liesenfeld; Nina Habermann; Robert W Owen; Augustin Scalbert; Cornelia M Ulrich Journal: Cancer Epidemiol Biomarkers Prev Date: 2013-10-04 Impact factor: 4.254
Authors: Erin M Siegel; Cornelia M Ulrich; Elizabeth M Poole; Rebecca S Holmes; Paul B Jacobsen; David Shibata Journal: Cancer Control Date: 2010-01 Impact factor: 3.302
Authors: David Croft; Antonio Fabregat Mundo; Robin Haw; Marija Milacic; Joel Weiser; Guanming Wu; Michael Caudy; Phani Garapati; Marc Gillespie; Maulik R Kamdar; Bijay Jassal; Steven Jupe; Lisa Matthews; Bruce May; Stanislav Palatnik; Karen Rothfels; Veronica Shamovsky; Heeyeon Song; Mark Williams; Ewan Birney; Henning Hermjakob; Lincoln Stein; Peter D'Eustachio Journal: Nucleic Acids Res Date: 2013-11-15 Impact factor: 16.971
Authors: Claire J Han; Biljana Gigic; Martin Schneider; Yakup Kulu; Anita R Peoples; Jennifer Ose; Torsten Kölsch; Paul B Jacobsen; Graham A Colditz; Jane C Figueiredo; William M Grady; Christopher I Li; David Shibata; Erin M Siegel; Adetunji T Toriola; Alexis B Ulrich; Karen L Syrjala; Cornelia M Ulrich Journal: J Cancer Surviv Date: 2020-03-12 Impact factor: 4.442
Authors: Cornelia M Ulrich; Mary Playdon; Rama Kiblawi; Andreana N Holowatyj; Biljana Gigic; Stefanie Brezina; Anne J M R Geijsen; Jennifer Ose; Tengda Lin; Sheetal Hardikar; Caroline Himbert; Christy A Warby; Jürgen Böhm; Martijn J L Bours; Fränzel J B van Duijnhoven; Tanja Gumpenberger; Dieuwertje E Kok; Janna L Koole; Eline H van Roekel; Petra Schrotz-King; Arve Ulvik; Andrea Gsur; Nina Habermann; Matty P Weijenberg; Per Magne Ueland; Martin Schneider; Alexis Ulrich Journal: Br J Nutr Date: 2020-02-05 Impact factor: 3.718
Authors: Justin C Brown; Bette J Caan; Carla M Prado; Elizabeth M Cespedes Feliciano; Jingjie Xiao; Candyce H Kroenke; Jeffrey A Meyerhardt Journal: J Natl Cancer Inst Date: 2020-04-01 Impact factor: 13.506
Authors: Cornelia M Ulrich; Biljana Gigic; Graham A Colditz; Jane C Figueiredo; William M Grady; Christopher I Li; David Shibata; Erin M Siegel; Adetunji T Toriola; Alexis Ulrich; Jürgen Böhm; Jennifer Ose; Richard Viskochil; Martin Schneider Journal: Cancer Epidemiol Biomarkers Prev Date: 2018-12-06 Impact factor: 4.254
Authors: Caroline Himbert; Mahmoud Delphan; Dominique Scherer; Laura W Bowers; Stephen Hursting; Cornelia M Ulrich Journal: Cancer Prev Res (Phila) Date: 2017-09
Authors: Erikka Loftfield; Emily Vogtmann; Joshua N Sampson; Steven C Moore; Heidi Nelson; Rob Knight; Nicholas Chia; Rashmi Sinha Journal: Cancer Epidemiol Biomarkers Prev Date: 2016-08-19 Impact factor: 4.254