{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T19:17:05Z","timestamp":1791314225292,"version":"4.3.1"},"reference-count":32,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2015,3,31]],"date-time":"2015-03-31T00:00:00Z","timestamp":1427760000000},"content-version":"vor","delay-in-days":30,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"crossref","award":["C1128\/A7309"],"award-info":[{"award-number":["C1128\/A7309"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2015,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      One hundred seven patients (15 weight\u2010stable healthy controls (HC) and 92 UGIC patients) were recruited. Mean (standard deviation) weight\u2010loss of UGIC patients was 8.1 (9.3%). Cachexia was defined as weight\u2010loss \u22655%.\n                      <jats:italic>Rectus\u2009abdominis<\/jats:italic>\n                      muscle was obtained at surgery and was analysed by western blotting or quantitative real\u2010time\u2013polymerase chain reaction. Candidate markers were selected according to previous literature and included Akt and phosphorylated Akt (pAkt,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200952), forkhead box O transcription factors (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200959), ubiquitin E3 ligases (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200959, control of muscle anabolism\/catabolism), BNIP3 and GABARAPL1 (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200959, as markers of autophagy), myosin heavy\u2010chain (MyHC,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200954), dystrophin (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200939),\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2010dystroglycan (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200952), and\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2010sarcoglycan (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200952, as markers of structural alteration in a muscle). Patients were followed up for an average of 1255\u2009days (range 581\u20131955\u2009days) or until death. Patients were grouped accordingly and analysed by (i) all cancer patients vs. HC; (ii) cachectic vs. non\u2010cachectic cancer patients; and (iii) cancer patients surviving \u22641 vs. &gt;1\u2009year post operatively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Cancer compared with HC patients had reduced mean (standard deviation) total Akt protein [0.49 (0.31) vs. 0.89 (0.17),\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.001], increased ratio of phosphorylated to total Akt [1.33 (1.04) vs. 0.32 (0.21), P\u2009=\u20090.002] and increased expression of GABARAPL1 [1.60 (0.76) vs. 1.10 (0.57),\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.024].\n                      <jats:italic>\n                        <jats:styled-content>\u03b2<\/jats:styled-content>\n                      <\/jats:italic>\n                      \u2010Dystroglycan levels were higher in cachectic compared with non\u2010cachectic cancer patients [1.01 (0.16) vs. 0.87 (0.20),\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.007]. Survival was shortened in patients with low compared with high MyHC levels (median 316 vs. 1326\u2009days,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.023) and dystrophin levels (median 341 vs. 660\u2009days,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.008).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      The present study has identified intramuscular protein level of\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2010dystroglycan as a potential biomarker of cancer cachexia. Changes in the structural elements of muscle (MyHC or dystrophin) appear to be survival biomarkers.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.12005","type":"journal-article","created":{"date-parts":[[2015,4,1]],"date-time":"2015-04-01T02:52:15Z","timestamp":1427856735000},"page":"53-61","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":68,"title":["Evaluating potential biomarkers of cachexia and survival in skeletal muscle of upper gastrointestinal cancer patients"],"prefix":"10.1002","volume":"6","author":[{"given":"Nathan A.","family":"Stephens","sequence":"first","affiliation":[{"name":"Department of Clinical and Surgical Sciences (Surgery), School of Clinical Sciences University of Edinburgh  Royal Infirmary, 51 Little France Crescent Edinburgh EH16 4SA UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard J. E.","family":"Skipworth","sequence":"additional","affiliation":[{"name":"Department of Clinical and Surgical Sciences (Surgery), School of Clinical Sciences University of Edinburgh  Royal Infirmary, 51 Little France Crescent Edinburgh EH16 4SA UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iain J.","family":"Gallagher","sequence":"additional","affiliation":[{"name":"Department of Clinical and Surgical Sciences (Surgery), School of Clinical Sciences University of Edinburgh  Royal Infirmary, 51 Little France Crescent Edinburgh EH16 4SA UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn A.","family":"Greig","sequence":"additional","affiliation":[{"name":"Department of Clinical and Surgical Sciences (Surgery), School of Clinical Sciences University of Edinburgh  Royal Infirmary, 51 Little France Crescent Edinburgh EH16 4SA UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denis C.","family":"Guttridge","sequence":"additional","affiliation":[{"name":"Division of Human Cancer Genetics The Ohio State University Wexner Medical Center  410 W. 10th Ave. Columbus OH 43210 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James A.","family":"Ross","sequence":"additional","affiliation":[{"name":"Department of Clinical and Surgical Sciences (Surgery), School of Clinical Sciences University of Edinburgh  Royal Infirmary, 51 Little France Crescent Edinburgh EH16 4SA UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth C. H.","family":"Fearon","sequence":"additional","affiliation":[{"name":"Department of Clinical and Surgical Sciences (Surgery), School of Clinical Sciences University of Edinburgh  Royal Infirmary, 51 Little France Crescent Edinburgh EH16 4SA UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,3,31]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(10)70218-7"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12041-011-0027-4"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-06-3067"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/SPC.0b013e3283186be2"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6604828"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.03-0610com"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200420174"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1065874"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.4161\/auto.5633"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2007.09.009"},{"key":"e_1_2_8_12_1","first-page":"973","article-title":"Mass 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