{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T01:09:48Z","timestamp":1773018588160,"version":"3.50.1"},"reference-count":43,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T00:00:00Z","timestamp":1768694400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T00:00:00Z","timestamp":1768694400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Treatments for cancer cachexia, defined as involuntary weight and muscle mass loss leading to significant functional impairment, remain unavailable partly due to insufficient improvement of clinically meaningful outcomes in current trials. By reflecting downstream effects of cellular function, metabolomics may identify mechanisms contributing to poor functional performance. Previous metabolomic studies in cancer cachexia have identified alterations in amino acid metabolism with weight loss or low muscularity; none have examined perturbations with poor physical function. We hypothesized that distinct metabolic signals in plasma and muscle are associated with weight loss, low muscle mass, and impaired function in cancer cachexia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We enrolled patients planning elective laparotomy for gastrointestinal or genitourinary cancer. Handgrip strength (HGS), stair climb power (SCP), and fasting plasma were collected within 2\u2009weeks prior to surgery; rectus abdominis samples were obtained during surgery. Metabolomic perturbations associated with physical function (HGS, SCP), muscularity (lumbar cross\u2010sectional area \u2018CSA\u2019 from opportunistic CT), or weight loss (&gt;\u20095% over previous 6\u2009months) were examined in plasma and muscle. The Mann\u2013Whitney U\u2010test compared metabolite abundance between weight\u2010losing and weight\u2010stable patients, while Spearman's correlation tested associations of abundance with CSA, HGS, or SCP. The \u2018Globaltest\u2019 method assessed pathway alterations with weight loss, CSA, HGS, or SCP; the Benjamini\u2010Hochberg adjustment was used to control for false discovery.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Patients (\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u200972) were male, median age 65 [interquartile range: 59\u201370], with 57% genitourinary cancer. Plasma and skeletal muscle metabolomic data were collected (\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u200964 and\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u200968, respectively). Weight loss was associated with significantly altered microbial, amino acid\/derivative, fatty acid\/lipid, and caffeine\u2010related metabolism pathways in plasma (adjusted\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.1). Lower CSA was associated with significantly altered fatty acid\/lipid, galactose, glycerophospholipid, and histidine metabolism and bile secretion pathways in skeletal muscle (adjusted\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.1). Worse HGS was nominally associated with altered plasma branched chain amino acid biosynthesis and altered skeletal muscle glutathione metabolism (unadjusted\n                      <jats:italic>p<\/jats:italic>\n                      \u2009\u2264\u20090.05), while worse SCP was nominally associated with altered skeletal muscle amino sugar\/nucleotide sugar metabolism and phenylalanine, tyrosine, and tryptophan biosynthesis (unadjusted\n                      <jats:italic>p<\/jats:italic>\n                      \u2009\u2264\u20090.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Significant metabolomic alterations in plasma and skeletal muscle characterized cancer\u2010related weight loss and reduced CSA, respectively. Nominal, function\u2010specific alterations were detected with worse HGS and SCP, which were distinct from those associated with weight loss or low CSA. Future larger studies may further characterize metabolomic profiles related to various functional outcomes and guide development of therapeutic targets to improve functional performance.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.70183","type":"journal-article","created":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T07:47:27Z","timestamp":1768808847000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Distinct Metabolomic Alterations Are Associated With Physical Function, Weight Loss, and Muscle Mass in Men With Cancer"],"prefix":"10.1002","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3810-2427","authenticated-orcid":false,"given":"Lindsey\u00a0J.","family":"Anderson","sequence":"first","affiliation":[{"name":"Geriatric Research, Education and Clinical Center Veterans Affairs Puget Sound Health Care System  Seattle Washington USA"},{"name":"Department of Medicine, Division of Gerontology and Geriatric Medicine University of Washington  Seattle Washington USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lu","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Statistics and Probability Michigan State University  East Lansing Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haiming","family":"Kerr","sequence":"additional","affiliation":[{"name":"Geriatric Research, Education and Clinical Center Veterans Affairs Puget Sound Health Care System  Seattle Washington USA"},{"name":"Department of Medicine, Division of Gerontology and Geriatric Medicine University of Washington  Seattle Washington USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marin","family":"Cabrera","sequence":"additional","affiliation":[{"name":"Geriatric Research, Education and Clinical Center Veterans Affairs Puget Sound Health Care System  Seattle Washington USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabien","family":"Chu","sequence":"additional","affiliation":[{"name":"Geriatric Research, Education and Clinical Center Veterans Affairs Puget Sound Health Care System  Seattle Washington USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaqueline","family":"Rose","sequence":"additional","affiliation":[{"name":"Geriatric Research, Education and Clinical Center Veterans Affairs Puget Sound Health Care System  Seattle Washington USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter\u00a0C.","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Surgery University of Washington  Seattle Washington USA"},{"name":"Department of Surgery Veterans Affairs Puget Sound Health Care System  Seattle Washington USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Atreya","family":"Dash","sequence":"additional","affiliation":[{"name":"Department of Urology Veterans Affairs Puget Sound Health Care System  Seattle Washington USA"},{"name":"Department of Urology University of Washington  Seattle Washington USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sina\u00a0A.","family":"Gharib","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Critical Care and Sleep Medicine University of Washington  Seattle Washington USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4245-1753","authenticated-orcid":false,"given":"Jose\u00a0M.","family":"Garcia","sequence":"additional","affiliation":[{"name":"Geriatric Research, Education and Clinical Center Veterans Affairs Puget Sound Health Care System  Seattle Washington USA"},{"name":"Department of Medicine, Division of Gerontology and Geriatric Medicine University of Washington  Seattle Washington USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,1,18]]},"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\/s11912-017-0562-0"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/SPC.0000000000000299"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(13)70055-X"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(14)71154-4"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12126"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12295"},{"issue":"2","key":"e_1_2_8_9_1","article-title":"Results From Two Phase 3 Randomized Trials of Enobosarm, Selective Androgen Receptor Modulator (SARM), for the Prevention and Treatment of Muscle Wasting in NSCLC","volume":"49","author":"Crawford J. 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