Please use this identifier to cite or link to this item: http://hdl.handle.net/1893/23094
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dc.contributor.authorStephens, Nathanen_UK
dc.contributor.authorSkipworth, Richard J Een_UK
dc.contributor.authorGallagher, Iain Jen_UK
dc.contributor.authorGreig, Carolynen_UK
dc.contributor.authorGuttridge, Denis Cen_UK
dc.contributor.authorRoss, James Aen_UK
dc.contributor.authorFearon, Kenneth C Hen_UK
dc.date.accessioned2018-01-20T01:58:32Z-
dc.date.available2018-01-20T01:58:32Z-
dc.date.issued2015-03en_UK
dc.identifier.urihttp://hdl.handle.net/1893/23094-
dc.description.abstractBackground  In order to grow the potential therapeutic armamentarium in the cachexia domain of supportive oncology, there is a pressing need to develop suitable biomarkers and potential drug targets. This pilot study evaluated several potential candidate biomarkers in skeletal muscle biopsies from a cohort of upper gastrointestinal cancer (UGIC) patients.  Methods  One hundred seven patients (15 weight-stable healthy controls (HC) and 92 UGIC patients) were recruited. Mean (standard deviation) weight-loss of UGIC patients was 8.1 (9.3\%). Cachexia was defined as weight-loss ≥5\%. Rectus abdominis muscle was obtained at surgery and was analysed by western blotting or quantitative real-time–polymerase chain reaction. Candidate markers were selected according to previous literature and included Akt and phosphorylated Akt (pAkt, n = 52), forkhead box O transcription factors (n = 59), ubiquitin E3 ligases (n = 59, control of muscle anabolism/catabolism), BNIP3 and GABARAPL1 (n = 59, as markers of autophagy), myosin heavy-chain (MyHC, n = 54), dystrophin (n = 39), β-dystroglycan (n = 52), and β-sarcoglycan (n = 52, as markers of structural alteration in a muscle). Patients were followed up for an average of 1255 days (range 581–1955 days) or until death. Patients were grouped accordingly and analysed by (i) all cancer patients vs. HC; (ii) cachectic vs. non-cachectic cancer patients; and (iii) cancer patients surviving ≤1 vs. {\textgreater}1 year post operatively.  Results  Cancer compared with HC patients had reduced mean (standard deviation) total Akt protein [0.49 (0.31) vs. 0.89 (0.17), P = 0.001], increased ratio of phosphorylated to total Akt [1.33 (1.04) vs. 0.32 (0.21), P = 0.002] and increased expression of GABARAPL1 [1.60 (0.76) vs. 1.10 (0.57), P = 0.024]. β-Dystroglycan levels were higher in cachectic compared with non-cachectic cancer patients [1.01 (0.16) vs. 0.87 (0.20), P = 0.007]. Survival was shortened in patients with low compared with high MyHC levels (median 316 vs. 1326 days, P = 0.023) and dystrophin levels (median 341 vs. 660 days, P = 0.008).  Conclusions  The present study has identified intramuscular protein level of β-dystroglycan as a potential biomarker of cancer cachexia. Changes in the structural elements of muscle (MyHC or dystrophin) appear to be survival biomarkers.en_UK
dc.language.isoenen_UK
dc.publisherWiley-Blackwellen_UK
dc.relationStephens N, Skipworth RJE, Gallagher IJ, Greig C, Guttridge DC, Ross JA & Fearon KCH (2015) Evaluating potential biomarkers of cachexia and survival in skeletal muscle of upper gastrointestinal cancer patients. Journal of Cachexia, Sarcopenia and Muscle, 6 (1), pp. 53-61. https://doi.org/10.1002/jcsm.12005en_UK
dc.rights© 2015 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society of Sarcopenia, Cachexia and Wasting Disorders This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.en_UK
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en_UK
dc.subjectBiomarkersen_UK
dc.subjectCachexiaen_UK
dc.subjectCanceren_UK
dc.subjectSkeletal muscleen_UK
dc.subjectSurvivalen_UK
dc.titleEvaluating potential biomarkers of cachexia and survival in skeletal muscle of upper gastrointestinal cancer patientsen_UK
dc.typeJournal Articleen_UK
dc.identifier.doi10.1002/jcsm.12005en_UK
dc.identifier.pmid26136412en_UK
dc.citation.jtitleJournal of Cachexia, Sarcopenia and Muscleen_UK
dc.citation.issn2190-6009en_UK
dc.citation.issn2190-5991en_UK
dc.citation.volume6en_UK
dc.citation.issue1en_UK
dc.citation.spage53en_UK
dc.citation.epage61en_UK
dc.citation.publicationstatusPublisheden_UK
dc.citation.peerreviewedRefereeden_UK
dc.type.statusVoR - Version of Recorden_UK
dc.author.emaili.j.gallagher@stir.ac.uken_UK
dc.citation.date31/03/2015en_UK
dc.contributor.affiliationUniversity of Edinburghen_UK
dc.contributor.affiliationUniversity of Edinburghen_UK
dc.contributor.affiliationSporten_UK
dc.contributor.affiliationUniversity of Edinburghen_UK
dc.contributor.affiliationOhio State Universityen_UK
dc.contributor.affiliationUniversity of Edinburghen_UK
dc.contributor.affiliationUniversity of Edinburghen_UK
dc.identifier.isiWOS:000352819100005en_UK
dc.identifier.wtid572377en_UK
dc.contributor.orcid0000-0002-8630-7235en_UK
dc.date.accepted2014-09-10en_UK
dcterms.dateAccepted2014-09-10en_UK
dc.date.filedepositdate2016-04-28en_UK
rioxxterms.apcnot requireden_UK
rioxxterms.typeJournal Article/Reviewen_UK
rioxxterms.versionVoRen_UK
local.rioxx.authorStephens, Nathan|en_UK
local.rioxx.authorSkipworth, Richard J E|en_UK
local.rioxx.authorGallagher, Iain J|0000-0002-8630-7235en_UK
local.rioxx.authorGreig, Carolyn|en_UK
local.rioxx.authorGuttridge, Denis C|en_UK
local.rioxx.authorRoss, James A|en_UK
local.rioxx.authorFearon, Kenneth C H|en_UK
local.rioxx.projectInternal Project|University of Stirling|https://isni.org/isni/0000000122484331en_UK
local.rioxx.freetoreaddate2016-04-28en_UK
local.rioxx.licencehttp://creativecommons.org/licenses/by-nc-nd/4.0/|2016-04-28|en_UK
local.rioxx.filenameStephens et al. - 2015 - Evaluating potential biomarkers of cachexia and su.pdfen_UK
local.rioxx.filecount1en_UK
local.rioxx.source2190-5991en_UK
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