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Weight loss of 10% (moderate) and 20% (severe) was induced by injection of colon\u201026 cancer cells in 10\u2010week old Balb\/c mice. In moderate cachexia, enriched pathways reflected fibrin formation, integrin\/mitogen\u2010activated protein kinase (MAPK) signaling, and innate immune system, suggesting an acute phase response and fibrosis. These pathways remained enriched in severe cachexia; however, energy\u2010yielding pathways housed in mitochondria were prominent additions to the severe state. These enrichments suggest distinct muscle proteome expression patterns that differentiate cachexia severity. When analyzed with two other mouse models, eight differentially expressed targets were shared including serine protease inhibitor A3N (Serpina3n), synaptophysin\u2010like protein 2 (Sypl2), Isocitrate dehydrogenase [NAD] subunit alpha, mitochondrial (Idh3a), peroxisomal acyl\u2010coenzyme A oxidase 1 (Acox1), collagen alpha\u20101(VI) chain (Col6a1), myozenin 3 (Myoz3), UDP\u2010glucose pyrophosphorylase (Ugp2), and solute carrier family 41 member 3 (Slc41a3). Acox1 and Idh3a control lipid oxidation and NADH generation in the TCA cycle, respectively, and Col6a1 comprises part of type VI collagen with reported profibrotic functions, suggesting influential roles in cachexia. A potential target was identified in fragile X mental retardation syndrome\u2010related protein 1 (FXR1), an RNA\u2010binding protein not previously implicated in cancer cachexia. FXR1 decreased in cachexia and related linearly with weight change and myofiber size. These findings suggest distinct mechanisms associated with cachexia severity and potential biomarkers and therapeutic targets.<\/jats:p>","DOI":"10.1002\/pmic.202100157","type":"journal-article","created":{"date-parts":[[2022,3,15]],"date-time":"2022-03-15T05:59:40Z","timestamp":1647323980000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Skeletal muscle proteome expression differentiates severity of cancer cachexia in mice and identifies loss of fragile X mental retardation syndrome\u2010related protein 1"],"prefix":"10.1002","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4449-536X","authenticated-orcid":false,"given":"Andy V.","family":"Khamoui","sequence":"first","affiliation":[{"name":"Department of Exercise Science and Health Promotion Florida Atlantic University  Boca Raton FL USA"},{"name":"Institute for Human Health and Disease Intervention Florida Atlantic University  Jupiter FL 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