{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T16:01:46Z","timestamp":1792425706803,"version":"4.5.0"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,3,15]],"date-time":"2023-03-15T00:00:00Z","timestamp":1678838400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010890","name":"Chinese Government Scholarship","doi-asserted-by":"publisher","award":["CSC No. 201806820029"],"award-info":[{"award-number":["CSC No. 201806820029"]}],"id":[{"id":"10.13039\/501100010890","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Cancer cachexia is a multifactorial syndrome characterized by body weight loss and systemic inflammation. The characterization of the inflammatory response in patients with cachexia is still limited. Lipocalin-2, a protein abundant in neutrophils, has recently been implicated in appetite suppression in preclinical models of pancreatic cancer cachexia. We hypothesized that lipocalin-2 levels could be associated with neutrophil activation and nutritional status of pancreatic ductal adenocarcinoma (PDAC) patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Plasma levels of neutrophil activation markers calprotectin, myeloperoxidase, elastase, and bactericidal\/permeability-increasing protein (BPI) were compared between non-cachectic PDAC patients (n=13) and cachectic PDAC patients with high (\u226526.9 ng\/mL, <jats:italic>n<\/jats:italic>=34) or low (&amp;lt;26.9 ng\/mL, <jats:italic>n<\/jats:italic>=34) circulating lipocalin-2 levels. Patients\u2019 nutritional status was assessed by the patient-generated subjective global assessment (PG-SGA) and through body composition analysis using CT-scan slices at the L3 level.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Circulating lipocalin-2 levels did not differ between cachectic and non-cachectic PDAC patients (median 26.7 (IQR 19.7-34.8) <jats:italic>vs<\/jats:italic>. 24.8 (16.6-29.4) ng\/mL, <jats:italic>p<\/jats:italic>=0.141). Cachectic patients with high systemic lipocalin-2 levels had higher concentrations of calprotectin, myeloperoxidase, and elastase than non-cachectic patients or cachectic patients with low lipocalin-2 levels (calprotectin: 542.3 (355.8-724.9) <jats:italic>vs<\/jats:italic>. 457.5 (213.3-606.9), <jats:italic>p<\/jats:italic>=0.448 <jats:italic>vs<\/jats:italic>. 366.5 (294.5-478.5) ng\/mL, <jats:italic>p<\/jats:italic>=0.009; myeloperoxidase: 30.3 (22.1-37.9) <jats:italic>vs<\/jats:italic>. 16.3 (12.0-27.5), <jats:italic>p<\/jats:italic>=0.021 <jats:italic>vs<\/jats:italic>. 20.2 (15.0-29.2) ng\/mL, <jats:italic>p<\/jats:italic>=0.011; elastase: 137.1 (90.8-253.2) <jats:italic>vs<\/jats:italic>. 97.2 (28.8-215.7), <jats:italic>p<\/jats:italic>=0.410 <jats:italic>vs<\/jats:italic>. 95.0 (72.2-113.6) ng\/mL, <jats:italic>p<\/jats:italic>=0.006; respectively). The CRP\/albumin ratio was also higher in cachectic patients with high lipocalin-2 levels (2.3 (1.3-6.0) as compared to non-cachectic patients (1.0 (0.7-4.2), <jats:italic>p<\/jats:italic>=0.041). Lipocalin-2 concentrations correlated with those of calprotectin (<jats:italic>r<jats:sub>s<\/jats:sub><\/jats:italic>=0.36, <jats:italic>p<\/jats:italic>&amp;lt;0.001), myeloperoxidase (<jats:italic>r<jats:sub>s<\/jats:sub><\/jats:italic>=0.48, <jats:italic>p<\/jats:italic>&amp;lt;0.001), elastase (<jats:italic>r<jats:sub>s<\/jats:sub><\/jats:italic>=0.50, <jats:italic>p<\/jats:italic>&amp;lt;0.001), and BPI (<jats:italic>r<jats:sub>s<\/jats:sub><\/jats:italic>=0.22, <jats:italic>p<\/jats:italic>=0.048). Whereas no significant correlations with weight loss, BMI, or L3 skeletal muscle index were observed, lipocalin-2 concentrations were associated with subcutaneous adipose tissue index (<jats:italic>r<jats:sub>s<\/jats:sub><\/jats:italic>=-0.25, <jats:italic>p<\/jats:italic>=0.034). Moreover, lipocalin-2 tended to be elevated in severely malnourished patients compared with well-nourished patients (27.2 (20.3-37.2) <jats:italic>vs<\/jats:italic>. 19.9 (13.4-26.4) ng\/mL, <jats:italic>p<\/jats:italic>=0.058).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These data suggest that lipocalin-2 levels are associated with neutrophil activation in patients with pancreatic cancer cachexia and that it may contribute to their poor nutritional status.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2023.1159411","type":"journal-article","created":{"date-parts":[[2023,3,15]],"date-time":"2023-03-15T05:36:20Z","timestamp":1678858580000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["Lipocalin-2 and neutrophil activation in pancreatic cancer cachexia"],"prefix":"10.3389","volume":"14","author":[{"given":"Min","family":"Deng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merel R.","family":"Aberle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annemarie A. 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