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Data are lacking on differences in these metrics based on PDAC anatomic location. We hypothesize that the primary tumour's anatomic region influences the prevalence and severity of unintentional weight loss.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Treatment na\u00efve patients with PDAC who underwent pancreatectomy at a single institution between 2012 and 2020 were identified retrospectively. Patients with pancreatic head or distal tumours were matched by sex, age, N and T stage. Serologic and anthropometric variables were obtained at the time of diagnosis. Skeletal muscle index (SMI), muscle radiation attenuation (MRA) and adiposity were measured. The primary outcome was presence of significant weight loss [&gt;5% body weight (BW) loss in past 6\u00a0months]. Signed rank tests, Cochran Mantel Haenszel tests and Kaplan\u2013Meier survival analysis are presented. RNA\u2010seq of tumours was performed to explore enriched pathways related to cachexia and weight loss.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Pancreatic head tumours (<jats:italic>n<\/jats:italic>\u00a0=\u00a024) were associated with higher prevalence (70.8% vs. 41.7%, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.081) and degree of weight loss (7.9% vs. 2.5%, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.014) compared to distal tumours (<jats:italic>n<\/jats:italic>\u00a0=\u00a024). BMI (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.642), SMI (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.738) and MRA (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.478) were similar between groups. Combining BW loss, SMI and MRA into a composite score, patients with pancreatic head cancers met more criteria associated with poor prognosis (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.142). Serum albumin (3.9 vs. 4.4\u00a0g\/dL, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.002) was lower and bilirubin (4.5 vs. 0.4\u00a0mg\/dL, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001) were higher with pancreatic head tumours. Survival differed by tumour location (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.014) with numerically higher median overall survival with distal tumours (11.1 vs. 21.8\u00a0months; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.066). Transcriptomic analysis revealed inactivation of appetite stimulation, weight regulation and nutrient digestion\/metabolism pathways in pancreatic head tumours.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Resectable pancreatic head PDAC is associated with higher prevalence of significant weight loss and more poor prognosis features. Pancreaticobiliary obstruction and hypoalbuminemia in patients with head tumours suggests compounding effects of nutrient malabsorption and systemic inflammation on molecular drivers of cachexia, possibly contributing to shorter survival. Therefore, PDAC\u2010associated cachexia is a heterogenous syndrome, which may be influenced by the primary tumour location. Select patients with resectable pancreatic head tumours may benefit from nutritional rehabilitation to improve outcomes.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.13390","type":"journal-article","created":{"date-parts":[[2023,12,21]],"date-time":"2023-12-21T00:58:30Z","timestamp":1703120310000},"page":"149-158","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Heterogeneity of weight loss and transcriptomic signatures in pancreatic ductal adenocarcinoma"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2088-5400","authenticated-orcid":false,"given":"Andrea N.","family":"Riner","sequence":"first","affiliation":[{"name":"Department of Surgery University of Florida College of Medicine  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly M.","family":"Herremans","sequence":"additional","affiliation":[{"name":"Department of Surgery University of Florida College of Medicine  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vignesh","family":"Vudatha","sequence":"additional","affiliation":[{"name":"Department of Surgery Virginia Commonwealth University  Richmond Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Surgery University of Florida College of Medicine  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xufeng","family":"Qu","sequence":"additional","affiliation":[{"name":"Department of Biostatistics Virginia Commonwealth University  Richmond Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinze","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biostatistics Virginia Commonwealth University  Richmond Virginia 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