Mariam Haffa1,2,3, Andreana N Holowatyj4,5, Mario Kratz6, Reka Toth3,7, Axel Benner8, Biljana Gigic3,9, Nina Habermann3,10, Petra Schrotz-King3, Jürgen Böhm3,4,5, Hermann Brenner3,11, Martin Schneider9, Alexis Ulrich9, Esther Herpel12,13, Peter Schirmacher13, Beate K Straub13,14, Johanna Nattenmüller15, Hans-Ulrich Kauczor15, Tengda Lin4,5, Claudia R Ball1,2,16, Cornelia M Ulrich3,4,5, Hanno Glimm1,2,16,17, Dominique Scherer3,18. 1. Division of Translational Functional Cancer Genomics, National Center for Tumor Diseases Heidelberg and German Cancer Research Center, Heidelberg, Germany. 2. Division of Translational Medical Oncology, National Center for Tumor Diseases Dresden and German Cancer Research Center, Dresden, Germany. 3. Division of Preventive Oncology, National Center for Tumor Diseases Heidelberg and German Cancer Research Center, Heidelberg, Germany. 4. Huntsman Cancer Institute, Salt Lake City, Utah. 5. Department of Population Health Sciences, University of Utah, Salt Lake City, Utah. 6. Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington. 7. Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center, Heidelberg, Germany. 8. Division of Biostatistics, German Cancer Research Center, Heidelberg, Germany. 9. Department of General, Visceral, and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany. 10. Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany. 11. Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany. 12. NCT Tissue Bank, National Center for Tumor Diseases and University Hospital Heidelberg, Heidelberg, Germany. 13. Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany. 14. Institute of Pathology, University Medicine Mainz, Mainz, Germany. 15. Department of Diagnostic and Interventional Radiology, University Hospital Heidelberg, Heidelberg, Germany. 16. Center for Personalized Oncology, University Hospital Carl Gustav Carus Dresden, Technische Universität Dresden, Dresden, Germany. 17. DKTK, Dresden, Germany. 18. Institute of Medical Biometry and Informatics, University Heidelberg, Heidelberg, Germany.
Abstract
CONTEXT: Adipose tissue inflammation and dysregulated energy homeostasis are key mechanisms linking obesity and cancer. Distinct adipose tissue depots strongly differ in their metabolic profiles; however, comprehensive studies of depot-specific perturbations among patients with cancer are lacking. OBJECTIVE: We compared transcriptome profiles of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) from patients with colorectal cancer and assessed the associations of different anthropometric measures with depot-specific gene expression. DESIGN: Whole transcriptomes of VAT and SAT were measured in 233 patients from the ColoCare Study, and visceral and subcutaneous fat area were quantified via CT. RESULTS: VAT compared with SAT showed elevated gene expression of cytokines, cell adhesion molecules, and key regulators of metabolic homeostasis. Increased fat area was associated with downregulated lipid and small molecule metabolism and upregulated inflammatory pathways in both compartments. Comparing these patterns between depots proved specific and more pronounced gene expression alterations in SAT and identified unique associations of integrins and lipid metabolism-related enzymes. VAT gene expression patterns that were associated with visceral fat area poorly overlapped with patterns associated with self-reported body mass index (BMI). However, subcutaneous fat area and BMI showed similar associations with SAT gene expression. CONCLUSIONS: This large-scale human study demonstrates pronounced disparities between distinct adipose tissue depots and reveals that BMI poorly correlates with fat mass-associated changes in VAT. Taken together, these results provide crucial evidence for the necessity to differentiate between distinct adipose tissue depots for a correct characterization of gene expression profiles that may affect metabolic health of patients with colorectal cancer.
CONTEXT: Adipose tissue inflammation and dysregulated energy homeostasis are key mechanisms linking obesity and cancer. Distinct adipose tissue depots strongly differ in their metabolic profiles; however, comprehensive studies of depot-specific perturbations among patients with cancer are lacking. OBJECTIVE: We compared transcriptome profiles of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) from patients with colorectal cancer and assessed the associations of different anthropometric measures with depot-specific gene expression. DESIGN: Whole transcriptomes of VAT and SAT were measured in 233 patients from the ColoCare Study, and visceral and subcutaneous fat area were quantified via CT. RESULTS: VAT compared with SAT showed elevated gene expression of cytokines, cell adhesion molecules, and key regulators of metabolic homeostasis. Increased fat area was associated with downregulated lipid and small molecule metabolism and upregulated inflammatory pathways in both compartments. Comparing these patterns between depots proved specific and more pronounced gene expression alterations in SAT and identified unique associations of integrins and lipid metabolism-related enzymes. VAT gene expression patterns that were associated with visceral fat area poorly overlapped with patterns associated with self-reported body mass index (BMI). However, subcutaneous fat area and BMI showed similar associations with SAT gene expression. CONCLUSIONS: This large-scale human study demonstrates pronounced disparities between distinct adipose tissue depots and reveals that BMI poorly correlates with fat mass-associated changes in VAT. Taken together, these results provide crucial evidence for the necessity to differentiate between distinct adipose tissue depots for a correct characterization of gene expression profiles that may affect metabolic health of patients with colorectal cancer.
Authors: Ruth Schübel; Johanna Nattenmüller; Disorn Sookthai; Tobias Nonnenmacher; Mirja E Graf; Lena Riedl; Christopher L Schlett; Oyunbileg von Stackelberg; Theron Johnson; Diana Nabers; Romy Kirsten; Mario Kratz; Hans-Ulrich Kauczor; Cornelia M Ulrich; Rudolf Kaaks; Tilman Kühn Journal: Am J Clin Nutr Date: 2018-11-01 Impact factor: 7.045
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: Kristin L Campbell; Karen E Foster-Schubert; Karen W Makar; Mario Kratz; Derek Hagman; Ellen A Schur; Nina Habermann; Marc Horton; Clare Abbenhardt; Ling-Yu Kuan; Liren Xiao; Jerry Davison; Martin Morgan; Ching-Yun Wang; Catherine Duggan; Anne McTiernan; Cornelia M Ulrich Journal: Cancer Prev Res (Phila) Date: 2013-01-22
Authors: Joakim Huber; Florian W Kiefer; Maximilian Zeyda; Bernhard Ludvik; Gerd R Silberhumer; Gerhard Prager; Gerhard J Zlabinger; Thomas M Stulnig Journal: J Clin Endocrinol Metab Date: 2008-05-20 Impact factor: 5.958
Authors: Brandon L Pierce; Rachel Ballard-Barbash; Leslie Bernstein; Richard N Baumgartner; Marian L Neuhouser; Mark H Wener; Kathy B Baumgartner; Frank D Gilliland; Bess E Sorensen; Anne McTiernan; Cornelia M Ulrich Journal: J Clin Oncol Date: 2009-05-26 Impact factor: 44.544
Authors: I Kralova Lesna; S Cejkova; A Kralova; J Fronek; M Petras; A Sekerkova; F Thieme; L Janousek; R Poledne Journal: Nutr Diabetes Date: 2017-04-10 Impact factor: 5.097
Authors: Michael W Greene; Peter T Abraham; Peyton C Kuhlers; Elizabeth A Lipke; Martin J Heslin; Stanley T Wijaya; Ifeoluwa Odeniyi Journal: PLoS One Date: 2022-05-13 Impact factor: 3.752
Authors: Andreana N Holowatyj; Mariam Haffa; Tengda Lin; Dominique Scherer; Biljana Gigic; Jennifer Ose; Christy A Warby; Caroline Himbert; Clare Abbenhardt-Martin; David Achaintre; Juergen Boehm; Kenneth M Boucher; Audrey Gicquiau; Andrea Gsur; Nina Habermann; Esther Herpel; Hans-Ulrich Kauczor; Pekka Keski-Rahkonen; Matthias Kloor; Magnus von Knebel-Doeberitz; Dieuwertje E Kok; Johanna Nattenmüller; Peter Schirmacher; Martin Schneider; Petra Schrotz-King; Thomas Simon; Per M Ueland; Richard Viskochil; Matty P Weijenberg; Augustin Scalbert; Alexis Ulrich; Laura W Bowers; Stephen D Hursting; Cornelia M Ulrich Journal: Cancer Prev Res (Phila) Date: 2020-07-12
Authors: Mariam Haffa; Andreana N Holowatyj; Mario Kratz; Reka Toth; Axel Benner; Biljana Gigic; Nina Habermann; Petra Schrotz-King; Jürgen Böhm; Hermann Brenner; Martin Schneider; Alexis Ulrich; Esther Herpel; Peter Schirmacher; Beate K Straub; Johanna Nattenmüller; Hans-Ulrich Kauczor; Tengda Lin; Claudia R Ball; Cornelia M Ulrich; Hanno Glimm; Dominique Scherer Journal: J Clin Endocrinol Metab Date: 2019-11-01 Impact factor: 5.958
Authors: Andreana N Holowatyj; Richard Viskochil; Dominik Ose; Benjamin Tingey; Benjamin Haaland; Dalton Wilson; Mikaela Larson; Sara Feltz; Mark A Lewis; Howard Colman; Cornelia M Ulrich Journal: J Adolesc Young Adult Oncol Date: 2020-07-29 Impact factor: 2.223
Authors: Vetri Sudar Jayaprakasam; Viktoriya Paroder; Peter Gibbs; Raazi Bajwa; Natalie Gangai; Ramon E Sosa; Iva Petkovska; Jennifer S Golia Pernicka; James Louis Fuqua; David D B Bates; Martin R Weiser; Andrea Cercek; Marc J Gollub Journal: Eur Radiol Date: 2021-07-29 Impact factor: 7.034
Authors: Heike Deutelmoser; Justo Lorenzo Bermejo; Axel Benner; Korbinian Weigl; Hanla A Park; Mariam Haffa; Esther Herpel; Martin Schneider; Cornelia M Ulrich; Michael Hoffmeister; Jenny Chang-Claude; Hermann Brenner; Dominique Scherer Journal: Int J Mol Sci Date: 2020-10-31 Impact factor: 5.923