Please use this identifier to cite or link to this item: http://hdl.handle.net/1893/31017
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dc.contributor.authorMiller, Janiceen_UK
dc.contributor.authorDreczkowski, Gillianen_UK
dc.contributor.authorRamage, Michael Ien_UK
dc.contributor.authorWigmore, Stephen Jen_UK
dc.contributor.authorGallagher, Iain Jen_UK
dc.contributor.authorSkipworth, Richard J Een_UK
dc.date.accessioned2020-04-21T00:01:44Z-
dc.date.available2020-04-21T00:01:44Z-
dc.date.issued2020-08en_UK
dc.identifier.urihttp://hdl.handle.net/1893/31017-
dc.description.abstractBackground Cancer cachexia is a poorly understood metabolic consequence of cancer. During cachexia, different adipose depots demonstrate differential wasting rates. Animal models suggest adipose tissue may be a key driver of muscle wasting through fat–muscle crosstalk, but human studies in this area are lacking. We performed global gene expression profiling of visceral (VAT) and subcutaneous (SAT) adipose from weight stable and cachectic cancer patients and healthy controls. Methods Cachexia was defined as >2% weight loss plus low computed tomography‐muscularity. Biopsies of SAT and VAT were taken from patients undergoing resection for oesophago‐gastric cancer, and healthy controls (n = 16 and 8 respectively). RNA was isolated and reverse transcribed. cDNA was hybridised to the Affymetrix Clariom S microarray and data analysed using R/Bioconductor. Differential expression of genes was assessed using empirical Bayes and moderated‐t‐statistic approaches. Category enrichment analysis was used with a tissue‐specific background to examine the biological context of differentially expressed genes. Selected differentially regulated genes were validated by qPCR. Enzyme‐linked immunosorbent assay (ELISA) for intelectin‐1 was performed on all VAT samples. The previously‐described cohort plus 12 additional patients from each group also had plasma I = intelectin‐1 ELISA carried out. Results In VAT vs. SAT comparisons, there were 2101, 1722, and 1659 significantly regulated genes in the cachectic, weight stable, and control groups, respectively. There were 2200 significantly regulated genes from VAT in cachectic patients compared with controls. Genes involving inflammation were enriched in cancer and control VAT vs. SAT, although different genes contributed to enrichment in each group. Energy metabolism, fat browning (e.g. uncoupling protein 1), and adipogenesis genes were down‐regulated in cancer VAT (P = 0.043, P = 5.4 × 10−6 and P = 1 × 10−6 respectively). The gene showing the largest difference in expression was ITLN1, the gene that encodes for intelectin‐1 (false discovery rate‐corrected P = 0.0001), a novel adipocytokine associated with weight loss in other contexts. Conclusions SAT and VAT have unique gene expression signatures in cancer and cachexia. VAT is metabolically active in cancer, and intelectin‐1 may be a target for therapeutic manipulation. VAT may play a fundamental role in cachexia, but the down‐regulation of energy metabolism genes implies a limited role for fat browning in cachectic patients, in contrast to pre‐clinical models.en_UK
dc.language.isoenen_UK
dc.publisherWiley Open Accessen_UK
dc.relationMiller J, Dreczkowski G, Ramage MI, Wigmore SJ, Gallagher IJ & Skipworth RJE (2020) Adipose depot gene expression and intelectin-1 in the metabolic response to cancer and cachexia. Journal of Cachexia, Sarcopenia and Muscle, 11 (4), pp. 1141-1153. https://doi.org/10.1002/jcsm.12568en_UK
dc.rights© 2020 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders This is an open access article under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited.en_UK
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_UK
dc.subjectCancer cachexiaen_UK
dc.subjectAdiposeen_UK
dc.subjectIntelectinen_UK
dc.subjectMicroarrayen_UK
dc.subjectGenesen_UK
dc.titleAdipose depot gene expression and intelectin-1 in the metabolic response to cancer and cachexiaen_UK
dc.typeJournal Articleen_UK
dc.identifier.doi10.1002/jcsm.12568en_UK
dc.identifier.pmid32232960en_UK
dc.citation.jtitleJournal of Cachexia, Sarcopenia and Muscleen_UK
dc.citation.issn2190-6009en_UK
dc.citation.issn2190-5991en_UK
dc.citation.volume11en_UK
dc.citation.issue4en_UK
dc.citation.spage1141en_UK
dc.citation.epage1153en_UK
dc.citation.publicationstatusPublisheden_UK
dc.citation.peerreviewedRefereeden_UK
dc.type.statusVoR - Version of Recorden_UK
dc.contributor.funderCancer Research UKen_UK
dc.citation.date31/03/2020en_UK
dc.contributor.affiliationUniversity of Edinburghen_UK
dc.contributor.affiliationSporten_UK
dc.contributor.affiliationUniversity of Edinburghen_UK
dc.contributor.affiliationUniversity of Edinburghen_UK
dc.contributor.affiliationSporten_UK
dc.contributor.affiliationUniversity of Edinburghen_UK
dc.identifier.isiWOS:000522276700001en_UK
dc.identifier.scopusid2-s2.0-85082514153en_UK
dc.identifier.wtid1603682en_UK
dc.contributor.orcid0000-0002-8630-7235en_UK
dc.date.accepted2020-02-25en_UK
dc.date.filedepositdate2020-04-20en_UK
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