@article{68bca52fdd224c9c9101a40fa5681a10,
title = "Multi-omics Analysis Reveals Adipose-tumor Crosstalk in Patients with Colorectal Cancer",
abstract = "Obesity and obesity-driven cancer rates are continuing to rise worldwide. We hypothesize that adipocyte-colonocyte interactions are a key driver of obesity-associated cancers. To understand the clinical relevance of visceral adipose tissue in advancing tumor growth, we analyzed paired tumoradjacent visceral adipose, normal mucosa, and colorectal tumor tissues as well as presurgery blood samples from patients with sporadic colorectal cancer. We report that high peroxisome proliferator-activated receptor gamma (PPARG) visceral adipose tissue expression is associated with glycoprotein VI (GPVI) signaling-the major signaling receptor for collagen-as well as fibrosis and adipogenesis pathway signaling in colorectal tumors. These associations were supported by correlations between PPARG visceral adipose tissue expression and circulating levels of plasma 4-hydroxyproline and serum intercellular adhesion molecule 1 (ICAM1), as well as gene set enrichment analysis and joint gene-metabolite pathway results integration that yielded significant enrichment of genes defining epithelialto-mesenchymal transition-as in fibrosis and metastasisand genes involved in glycolytic metabolism, confirmed this association. We also reveal that elevated prostaglandinendoperoxide synthase 2 (PTGS2) colorectal tumor expression is associated with a fibrotic signature in adipose-tumor crosstalk via GPVI signaling and dendritic cell maturation in visceral adipose tissue. Systemic metabolite and biomarker profiling confirmed that high PTGS2 expression in colorectal tumors is significantly associated with higher concentrations of serum amyloidAand glycine, and lower concentrations of sphingomyelin, in patients with colorectal cancer. This multi-omics study suggests that adipose-tumor crosstalk in patients with colorectal cancer is a critical microenvironment interaction that could be therapeutically targeted.",
keywords = "colon, expression, fat, inflammation, inhibition, modulation, obesity, risk, serum c-peptide, tissue macrophages, RISK, COLON, SERUM C-PEPTIDE, OBESITY, INHIBITION, INFLAMMATION, FAT, TISSUE MACROPHAGES, EXPRESSION, MODULATION",
author = "A.N. Holowatyj and M. Haffa and T.D. Lin and D. Scherer and B. Gigic and J. Ose and C.A. Warby and C. Himbert and C. Abbenhardt-Martin and D. Achaintre and J. Boehm and K.M. Boucher and A. Gicquiau and A. Gsur and N. Habermann and E. Herpel and H.U. Kauczor and P. Keski-Rahkonen and M. Kloor and {von Knebel-Doeberitz}, M. and D.E. Kok and J. Nattenmuller and P. Schirmacher and M. Schneider and P. Schrotz-King and T. Simon and P.M. Ueland and R. Viskochil and M.P. Weijenberg and A. Scalbert and A. Ulrich and L.W. Bowers and S.D. Hursting and C.M. Ulrich",
note = "Funding Information: A.N. Holowatyj was supported by the NIH under Ruth L. Kirschstein National Research Service Award T32 HG008962 from the National Human Genome Research Institute and by the Vanderbilt University Medical Center. This work was also supported by grants from the NIH/ NCI (U01 CA206110, R01 CA189184, R01 CA211705, and R01 CA207371 to C.M. Ulrich; R35 CA197627 to S.D. Hursting), the German Consortium of Translational Cancer Research (DKTK) and the German Cancer Research Center, the Matthias Lackas Foundation, Stiftung LebensBlicke, and Claussen-Simon Stiftung (Germany), the Huntsman Cancer Foundation, and the Immunology, Inflammation, and Infectious Disease Initiative Funding Information: A.N. Holowatyj reports grants from NIH, Huntsman Cancer Foundation, and University of Utah, Immunology, Inflammation, and Infectious Disease Initiative during the conduct of the study. J. Ose reports grants from NCI during the conduct of the study. C.A. Warby reports grants from NIH (received part of my salary from NIH grants) and other from Huntsman Foundation (received part of my salary from the Huntsman Foundation) during the conduct of the study. H.-U. Kauczor reports grants from Stiftung zur Forderung der Erforschung der Zivilisationserkrankungen during the conduct of the study; Ministerium fu€r Wissenschaft und Kunst Baden-Wu€rttemberg outside the submitted work. C.M. Ulrich reports that as center director she formally oversees research funded by a number of companies, including pharmaceutical companies. She has not received any funding for her own research or any funding that could be in conflict with the proposed work. No potential conflicts of interest were disclosed by the other authors. Publisher Copyright: {\textcopyright} 2020 American Association for Cancer Research.",
year = "2020",
month = oct,
day = "1",
doi = "10.1158/1940-6207.capr-19-0538",
language = "English",
volume = "13",
pages = "817--828",
journal = "Cancer prevention research",
issn = "1940-6207",
publisher = "American Association for Cancer Research Inc.",
number = "10",
}