{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T08:32:44Z","timestamp":1793349164602,"version":"4.5.0"},"reference-count":42,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T00:00:00Z","timestamp":1710288000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The interdependence of cytokines and appetite\u2010modifying hormones implicated in cancer anorexia\u2010cachexia syndrome (CACS) remains unclear. This study aimed to regroup these cytokines and hormones into distinct inflammatory (or non\u2010inflammatory) pathways and determine whether these pathways can classify patients with CACS phenotypes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Clinical characteristics of 133 patients [61.7% male; mean age\u00a0=\u00a063.4 (SD: 13.1) years] with advanced cancer prior to oncology treatments were documented, including weight loss history. Patients completed the Functional Assessment of Anorexia\u2010Cachexia Therapy (FAACT) questionnaire and Timed Up and Go test and had their sex\u2010standardized skeletal muscle index\u00a0(z\u2010SMI) and fat mass index (z\u2010FMI) derived using computed tomography scans. Their plasma levels of cytokines and appetite\u2010modifying hormones were also determined. Date of death was recorded. Exploratory factor analysis (EFA) was used to regroup 15 cytokines and hormone into distinct inflammatory pathways (factors). For each patient, regression factor scores (RFS), which tell how strongly the patient associates with each factor, were derived. Two\u2010step cluster analysis on the RFS was used to classify patients into groups. CACS phenotypes were correlated with RFS and compared between groups. Groups' survival was estimated using Kaplan\u2013Meier analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Patients had low z\u2010SMI (mean\u00a0=\u00a0\u22123.78\u00a0cm<jats:sup>2<\/jats:sup>\/m<jats:sup>2<\/jats:sup>; SD: 8.88) and z\u2010FMI (mean\u00a0=\u00a00.08\u00a0kg<jats:sup>2<\/jats:sup>\/m<jats:sup>2<\/jats:sup>; SD: 56.25), and 62 (46.6%) had cachexia. EFA identified three factors: (F\u20101) IFN\u2010\u03b3, IL\u20101\u03b2, Il\u20104, IL\u20106, IL\u201010, IL\u201012, TGF\u03b21 (positive contribution), and IL\u201018 (negative); (F\u20102) IL\u20108, IL\u201018, MCP\u20101, TGF\u03b21, TNF\u2010\u03b1 (positive), and ghrelin (negative); and (F\u20103) TRAIL and leptin (positive), and TGF\u03b21 and adiponectin (negative). RFS\u20101 was associated with cachexia (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.002); RFS\u20102, with higher CRP (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.0001) and decreased physical function (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.01); and RFS\u20103 with better appetite (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.04), lower CRP (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.002), higher z\u2010SMI (<jats:italic>P<\/jats:italic> = 0.04) and z\u2010FMI (<jats:italic>P<\/jats:italic> &lt; 0.0001), and less cachexia characteristics (all <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001). Four patient groups were identified with specific RFS clusters aligning with the CACS continuum from no cachexia to pre\u2010cachexia, cachexia, and terminal cachexia. Compared to the other two groups, groups 1 and 2 had higher plasma levels of IL\u201018 and TRAIL. Group 1 also had lower inflammatory cytokines, adiponectin, and CRP compared to the other three groups. Group 3 had inflammatory cytokine levels similar to group 2, except for TNF\u2010\u03b1 and leptin which were lower. Group 4 had very high inflammatory cytokines, adiponectin, and CRP compared to the other 3 groups (all <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.0001). Groups 3 and 4 had worse cachexia characteristics (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05) and shorter survival (log rank: <jats:italic>P<\/jats:italic>\u00a0=\u00a00.0009) than the other two groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This exploratory study identified three distinct pathways of inflammation, or lack thereof, characterizing different CACS phenotypes.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.13430","type":"journal-article","created":{"date-parts":[[2024,3,14]],"date-time":"2024-03-14T05:44:00Z","timestamp":1710395040000},"page":"1041-1053","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Cancer anorexia\u2010cachexia syndrome is characterized by more than one inflammatory pathway"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0843-0366","authenticated-orcid":false,"given":"Bruno","family":"Gagnon","sequence":"first","affiliation":[{"name":"D\u00e9partement de m\u00e9decine familiale et de m\u00e9decine d'urgence, Centre de recherche sur le cancer Universit\u00e9 Laval, Centre de recherche du CHU de Qu\u00e9bec  Qu\u00e9bec Canada"},{"name":"Division of Clinical Epidemiology McGill University Health Centre  Montreal Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8071-4457","authenticated-orcid":false,"given":"Jessica","family":"Murphy","sequence":"additional","affiliation":[{"name":"Division of Clinical Epidemiology McGill University Health Centre  Montreal Canada"},{"name":"Department of Health, Kinesiology, and Applied Physiology Concordia University  Montreal Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8826-7428","authenticated-orcid":false,"given":"David","family":"Simonyan","sequence":"additional","affiliation":[{"name":"Clinical and Evaluative Research Platform Universit\u00e9 Laval, Centre de recherche du CHU de Qu\u00e9bec  Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia A.","family":"Penafuerte","sequence":"additional","affiliation":[{"name":"Cura Therapeutics NEOMED Institute  Saint\u2010Laurent Canada"},{"name":"Rosalind and Morris Goodman Cancer Institute McGill University  Montreal Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacinthe","family":"Sirois","sequence":"additional","affiliation":[{"name":"Rosalind and Morris Goodman Cancer Institute McGill University  Montreal Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0406-9692","authenticated-orcid":false,"given":"Martin","family":"Chasen","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Family and Community Medicine University of Toronto  Toronto Canada"},{"name":"Department of Family Medicine McMaster University  Hamilton Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel L.","family":"Tremblay","sequence":"additional","affiliation":[{"name":"Rosalind and Morris Goodman Cancer Institute McGill University  Montreal 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