{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T08:10:22Z","timestamp":1790237422460,"version":"4.1.0"},"reference-count":85,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2020,12,15]],"date-time":"2020-12-15T00:00:00Z","timestamp":1607990400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R01-CA122596"],"award-info":[{"award-number":["R01-CA122596"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R01-CA194593"],"award-info":[{"award-number":["R01-CA194593"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["P30-CA082709"],"award-info":[{"award-number":["P30-CA082709"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01-DK096167"],"award-info":[{"award-number":["R01-DK096167"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005979","name":"Lustgarten Foundation","doi-asserted-by":"publisher","award":["No number"],"award-info":[{"award-number":["No number"]}],"id":[{"id":"10.13039\/100005979","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Heroes Foundation","award":["No number"],"award-info":[{"award-number":["No number"]}]},{"DOI":"10.13039\/100006976","name":"Lilly Endowment","doi-asserted-by":"publisher","award":["No number"],"award-info":[{"award-number":["No number"]}],"id":[{"id":"10.13039\/100006976","id-type":"DOI","asserted-by":"publisher"}]},{"name":"IUPUI Signature Center for Pancreatic Cancer Research","award":["No number"],"award-info":[{"award-number":["No number"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Patients with pancreatic ductal adenocarcinoma (PDAC) suffer debilitating and deadly weight loss, known as cachexia. Development of therapies requires biomarkers to diagnose, and monitor cachexia; however, no such markers are in use. Via Somascan, we measured ~1300 plasma proteins in 30 patients with PDAC vs. 11 controls. We found 60 proteins specific to local PDAC, 46 to metastatic, and 67 to presence of &gt;5% cancer weight loss (FC \u2265 |1.5|, p \u2264 0.05). Six were common for cancer stage (Up: GDF15, TIMP1, IL1RL1; Down: CCL22, APP, CLEC1B). Four were common for local\/cachexia (C1R, PRKCG, ELANE, SOST: all oppositely regulated) and four for metastatic\/cachexia (SERPINA6, PDGFRA, PRSS2, PRSS1: all consistently changed), suggesting that stage and cachexia status might be molecularly separable. We found 71 proteins that correlated with cachexia severity via weight loss grade, weight loss, skeletal muscle index and radiodensity (r \u2265 |0.50|, p \u2264 0.05), including some known cachexia mediators\/markers (LEP, MSTN, ALB) as well as novel proteins (e.g., LYVE1, C7, F2). Pathway, correlation, and upstream regulator analyses identified known (e.g., IL6, proteosome, mitochondrial dysfunction) and novel (e.g., Wnt signaling, NK cells) mechanisms. Overall, this study affords a basis for validation and provides insights into the processes underpinning cancer cachexia.<\/jats:p>","DOI":"10.3390\/cancers12123787","type":"journal-article","created":{"date-parts":[[2020,12,15]],"date-time":"2020-12-15T21:11:02Z","timestamp":1608066662000},"page":"3787","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Identification of Potential Serum Protein Biomarkers and Pathways for Pancreatic Cancer Cachexia Using an Aptamer-Based Discovery Platform"],"prefix":"10.3390","volume":"12","author":[{"given":"Ashok","family":"Narasimhan","sequence":"first","affiliation":[{"name":"Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Safi","family":"Shahda","sequence":"additional","affiliation":[{"name":"Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA"},{"name":"Simon and Bren Comprehensive Cancer Center, Indiana University, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua K.","family":"Kays","sequence":"additional","affiliation":[{"name":"Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan M.","family":"Perkins","sequence":"additional","affiliation":[{"name":"Simon and Bren Comprehensive Cancer Center, Indiana University, Indianapolis, IN 46202, USA"},{"name":"Department of Biostatistics, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijun","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katheryn N. H.","family":"Schloss","sequence":"additional","affiliation":[{"name":"Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel E. I.","family":"Schloss","sequence":"additional","affiliation":[{"name":"Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonidas G.","family":"Koniaris","sequence":"additional","affiliation":[{"name":"Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA"},{"name":"Indiana Center for Musculoskeletal Health, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7872-0540","authenticated-orcid":false,"given":"Teresa A.","family":"Zimmers","sequence":"additional","affiliation":[{"name":"Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA"},{"name":"Simon and Bren Comprehensive Cancer Center, Indiana University, Indianapolis, IN 46202, USA"},{"name":"Indiana Center for Musculoskeletal Health, Indianapolis, IN 46202, USA"},{"name":"Department of Otolaryngology\u2014Head &amp; Neck Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA"},{"name":"Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA"},{"name":"Richard L. Roudebush Veterans Administration Medical Center, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/S1470-2045(10)70218-7","article-title":"Definition and classification of cancer cachexia: An international consensus","volume":"12","author":"Fearon","year":"2011","journal-title":"Lancet Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"17105","DOI":"10.1038\/nrdp.2017.105","article-title":"Cancer-associated cachexia","volume":"4","author":"Baracos","year":"2018","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1200\/JCO.2014.56.1894","article-title":"Diagnostic criteria for the classification of cancer-associated weight loss","volume":"33","author":"Martin","year":"2015","journal-title":"J. Clin. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1097\/MPA.0000000000000898","article-title":"Predictors of Pancreatic Cancer-Associated Weight Loss and Nutritional Interventions","volume":"46","author":"Nemer","year":"2017","journal-title":"Pancreas"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"17","DOI":"10.21037\/jgo.2017.11.10","article-title":"Cachexia, and not obesity, prior to pancreatic cancer diagnosis worsens survival and is negated by chemotherapy","volume":"9","author":"Hendifar","year":"2018","journal-title":"J. Gastrointest. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Bieliuniene, E., Brondum Frokjaer, J., Pockevicius, A., Kemesiene, J., Lukosevicius, S., Basevicius, A., Atstupenaite, V., Barauskas, G., Ignatavicius, P., and Gulbinas, A. (2019). CT- and MRI-Based Assessment of Body Composition and Pancreatic Fibrosis Reveals High Incidence of Clinically Significant Metabolic Changes That Affect the Quality of Life and Treatment Outcomes of Patients with Chronic Pancreatitis and Pancreatic Cancer. Medicina, 55.","DOI":"10.3390\/medicina55100649"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Naumann, P., Eberlein, J., Farnia, B., Hackert, T., Debus, J., and Combs, S.E. (2019). Continued Weight Loss and Sarcopenia Predict Poor Outcomes in Locally Advanced Pancreatic Cancer Treated with Chemoradiation. Cancers, 11.","DOI":"10.3390\/cancers11050709"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1016\/j.pan.2019.07.039","article-title":"Characterising the impact of body composition change during neoadjuvant chemotherapy for pancreatic cancer","volume":"19","author":"Griffin","year":"2019","journal-title":"Pancreatology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1002\/jcsm.12307","article-title":"Three cachexia phenotypes and the impact of fat-only loss on survival in FOLFIRINOX therapy for pancreatic cancer","volume":"9","author":"Kays","year":"2018","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Naumann, P., Eberlein, J., Farnia, B., Liermann, J., Hackert, T., Debus, J., and Combs, S.E. (2019). Cachectic Body Composition and Inflammatory Markers Portend a Poor Prognosis in Patients with Locally Advanced Pancreatic Cancer Treated with Chemoradiation. Cancers, 11.","DOI":"10.3390\/cancers11111655"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1007\/s00520-019-04797-y","article-title":"Unintentional weight loss, its associated burden, and perceived weight status in people with cancer","volume":"28","author":"Yuen","year":"2020","journal-title":"Support. Care Cancer"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"432","DOI":"10.6004\/jnccn.2018.7111","article-title":"A Population-Based Study of Morbidity After Pancreatic Cancer Diagnosis","volume":"17","author":"Sarkar","year":"2019","journal-title":"J. Natl. Compr. Canc. Netw."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.semcdb.2016.02.009","article-title":"STAT3 in the systemic inflammation of cancer cachexia","volume":"54","author":"Zimmers","year":"2016","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2438","DOI":"10.1200\/JCO.20.00611","article-title":"Management of Cancer Cachexia: ASCO Guideline","volume":"38","author":"Roeland","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Bonetto, A., Rupert, J.E., Barreto, R., and Zimmers, T.A. (2016). The Colon-26 Carcinoma Tumor-bearing Mouse as a Model for the Study of Cancer Cachexia. J. Vis. Exp.","DOI":"10.3791\/54893"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1002\/jcsm.12461","article-title":"The systemic activin response to pancreatic cancer: Implications for effective cancer cachexia therapy","volume":"10","author":"Zhong","year":"2019","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"4682","DOI":"10.1038\/s41467-019-12657-w","article-title":"The TLR7\/8 agonist R848 remodels tumor and host responses to promote survival in pancreatic cancer","volume":"10","author":"Michaelis","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.canlet.2020.04.017","article-title":"Macrophages potentiate STAT3 signaling in skeletal muscles and regulate pancreatic cancer cachexia","volume":"484","author":"Shukla","year":"2020","journal-title":"Cancer Lett."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Burfeind, K.G., Zhu, X., Norgard, M.A., Levasseur, P.R., Huisman, C., Buenafe, A.C., Olson, B., Michaelis, K.A., Torres, E.R., and Jeng, S. (2020). Circulating myeloid cells invade the central nervous system to mediate cachexia during pancreatic cancer. eLife, 9.","DOI":"10.7554\/eLife.54095"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1612","DOI":"10.1016\/j.celrep.2019.07.016","article-title":"Modeling Human Cancer-induced Cachexia","volume":"28","author":"Talbert","year":"2019","journal-title":"Cell Rep."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1002\/jcsm.12077","article-title":"MAP3K11\/GDF15 axis is a critical driver of cancer cachexia","volume":"7","author":"Lerner","year":"2016","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_22","first-page":"682","article-title":"The MEK-Inhibitor Selumetinib Attenuates Tumor Growth and Reduces IL-6 Expression but Does Not Protect against Muscle Wasting in Lewis Lung Cancer Cachexia","volume":"7","author":"Au","year":"2016","journal-title":"Front. Physiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1548","DOI":"10.1016\/j.bbrc.2009.12.123","article-title":"Acute inhibition of myostatin-family proteins preserves skeletal muscle in mouse models of cancer cachexia","volume":"391","author":"Aydogdu","year":"2010","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Huot, J.R., Pin, F., Narasimhan, A., Novinger, L.J., Keith, A.S., Zimmers, T.A., Willis, M.S., and Bonetto, A. (2020). ACVR2B antagonism as a countermeasure to multi-organ perturbations in metastatic colorectal cancer cachexia. J. Cachexia Sarcopenia Muscle.","DOI":"10.1002\/jcsm.12642"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.1038\/s41591-020-0945-x","article-title":"Antibody-mediated inhibition of GDF15-GFRAL activity reverses cancer cachexia in mice","volume":"26","author":"Suriben","year":"2020","journal-title":"Nat. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1097\/MCO.0000000000000555","article-title":"Novel molecular targets of muscle wasting in cancer patients","volume":"22","author":"Miller","year":"2019","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1200\/JCO.2012.45.2722","article-title":"Cancer cachexia in the age of obesity: Skeletal muscle depletion is a powerful prognostic factor, independent of body mass index","volume":"31","author":"Martin","year":"2013","journal-title":"J. Clin. Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e201","DOI":"10.1038\/mtna.2014.49","article-title":"Nucleic Acid Ligands With Protein-like Side Chains: Modified Aptamers and Their Use as Diagnostic and Therapeutic Agents","volume":"3","author":"Rohloff","year":"2014","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"279","DOI":"10.4300\/JGME-D-12-00156.1","article-title":"Using Effect Size\u2014Or Why the P Value Is Not Enough","volume":"4","author":"Sullivan","year":"2012","journal-title":"J. Grad. Med. Educ."},{"key":"ref_30","first-page":"679","article-title":"Differential Bone Loss in Mouse Models of Colon Cancer Cachexia","volume":"7","author":"Bonetto","year":"2016","journal-title":"Front. Physiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.metabol.2014.08.004","article-title":"Physiology of leptin: Energy homeostasis, neuroendocrine function and metabolism","volume":"64","author":"Park","year":"2015","journal-title":"Metabolism"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1038\/nrc3829","article-title":"Cancer cachexia: Understanding the molecular basis","volume":"14","author":"Argiles","year":"2014","journal-title":"Nat. Rev. Cancer"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1002\/jcsm.12539","article-title":"Interleukin-4 administration improves muscle function, adult myogenesis, and lifespan of colon carcinoma-bearing mice","volume":"11","author":"Costamagna","year":"2020","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1002\/jcsm.12346","article-title":"Tumour-derived leukaemia inhibitory factor is a major driver of cancer cachexia and morbidity in C26 tumour-bearing mice","volume":"9","author":"Kandarian","year":"2018","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Takenaga, K., Akimoto, M., Koshikawa, N., and Nagase, H. (2020). Cancer cell-derived interleukin-33 decoy receptor sST2 enhances orthotopic tumor growth in a murine pancreatic cancer model. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0232230"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s12032-018-1223-3","article-title":"Plasma levels of interleukin-33 and soluble suppression of tumorigenicity 2 in patients with advanced pancreatic ductal adenocarcinoma undergoing systemic chemotherapy","volume":"36","author":"Kieler","year":"2018","journal-title":"Med. Oncol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.3389\/fgene.2019.01306","article-title":"Identification of Platform-Independent Diagnostic Biomarker Panel for Hepatocellular Carcinoma Using Large-Scale Transcriptomics Data","volume":"10","author":"Kaur","year":"2019","journal-title":"Front. Genet."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1016\/j.tranon.2018.02.010","article-title":"CLEC1B Expression and PD-L1 Expression Predict Clinical Outcome in Hepatocellular Carcinoma with Tumor Hemorrhage","volume":"11","author":"Hu","year":"2018","journal-title":"Transl. Oncol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"860","DOI":"10.18632\/oncotarget.6205","article-title":"GDF15 promotes EMT and metastasis in colorectal cancer","volume":"7","author":"Li","year":"2016","journal-title":"Oncotarget"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Peng, H., Pan, S., Yan, Y., Brand, R.E., Petersen, G.M., Chari, S.T., Lai, L.A., Eng, J.K., Brentnall, T.A., and Chen, R. (2020). Systemic Proteome Alterations Linked to Early Stage Pancreatic Cancer in Diabetic Patients. Cancers, 12.","DOI":"10.3390\/cancers12061534"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Prokopchuk, O., Grunwald, B., Nitsche, U., Jager, C., Prokopchuk, O.L., Schubert, E.C., Friess, H., Martignoni, M.E., and Kruger, A. (2018). Elevated systemic levels of the matrix metalloproteinase inhibitor TIMP-1 correlate with clinical markers of cachexia in patients with chronic pancreatitis and pancreatic cancer. BMC Cancer, 18.","DOI":"10.1186\/s12885-018-4055-9"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2158","DOI":"10.1002\/cncr.30057","article-title":"A novel systemic inflammation response index (SIRI) for predicting the survival of patients with pancreatic cancer after chemotherapy","volume":"122","author":"Qi","year":"2016","journal-title":"Cancer"},{"key":"ref_43","first-page":"7032","article-title":"Increased expression and processing of the Alzheimer amyloid precursor protein in pancreatic cancer may influence cellular proliferation","volume":"63","author":"Hansel","year":"2003","journal-title":"Cancer Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e12799","DOI":"10.1111\/acel.12799","article-title":"Plasma proteomic signature of age in healthy humans","volume":"17","author":"Tanaka","year":"2018","journal-title":"Aging Cell"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1843","DOI":"10.1038\/s41591-019-0673-2","article-title":"Undulating changes in human plasma proteome profiles across the lifespan","volume":"25","author":"Lehallier","year":"2019","journal-title":"Nat. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2030","DOI":"10.1210\/jc.2014-4318","article-title":"Role of Activin A and myostatin in human cancer cachexia","volume":"100","author":"Loumaye","year":"2015","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"4026","DOI":"10.1096\/fj.201901220R","article-title":"GASP-2 overexpressing mice exhibit a hypermuscular phenotype with contrasting molecular effects compared to GASP-1 transgenics","volume":"34","author":"Parente","year":"2020","journal-title":"FASEB J."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1038\/s41416-019-0694-0","article-title":"Development of PancRISK, a urine biomarker-based risk score for stratified screening of pancreatic cancer patients","volume":"122","author":"Blyuss","year":"2020","journal-title":"Br. J. Cancer"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"444","DOI":"10.2174\/1389202919666180221160753","article-title":"Genetic Alterations of Periampullary and Pancreatic Ductal Adenocarcinoma: An Overview","volume":"19","author":"Sikdar","year":"2018","journal-title":"Curr. Genom."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1089\/pancan.2019.0014","article-title":"Is There a Trojan Horse to Aggressive Pancreatic Cancer Biology? A Review of the Trypsin-PAR2 Axis to Proliferation, Early Invasion, and Metastasis","volume":"6","author":"Soreide","year":"2020","journal-title":"J. Pancreat. Cancer"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"5805","DOI":"10.1007\/s13277-015-3982-1","article-title":"PRSS1 mutations and the proteinase\/antiproteinase imbalance in the pathogenesis of pancreatic cancer","volume":"37","author":"Yi","year":"2016","journal-title":"Tumor Biol."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Nakanishi, T., Forgetta, V., Handa, T., Hirai, T., Mooser, V., Lathrop, M.G., Cookson, W., and Richards, J.B. (2020). The Undiagnosed Disease Burden Associated with Alpha-1 Antitrypsin Deficiency Genotypes. Eur. Respir. J.","DOI":"10.1164\/ajrccm-conference.2020.201.1_MeetingAbstracts.A7833"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Schwarz, S., Prokopchuk, O., Esefeld, K., Groschel, S., Bachmann, J., Lorenzen, S., Friess, H., Halle, M., and Martignoni, M.E. (2017). The clinical picture of cachexia: A mosaic of different parameters (experience of 503 patients). BMC Cancer, 17.","DOI":"10.1186\/s12885-017-3116-9"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Kim, E.Y., Kim, Y.S., Seo, J.Y., Park, I., Ahn, H.K., Jeong, Y.M., Kim, J.H., and Kim, N. (2016). The Relationship between Sarcopenia and Systemic Inflammatory Response for Cancer Cachexia in Small Cell Lung Cancer. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0161125"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1002\/jcsm.12331","article-title":"LY2495655, an antimyostatin antibody, in pancreatic cancer: A randomized, phase 2 trial","volume":"9","author":"Golan","year":"2018","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Fujiwara, Y., Kobayashi, T., Chayahara, N., Imamura, Y., Toyoda, M., Kiyota, N., Mukohara, T., Nishiumi, S., Azuma, T., and Yoshida, M. (2014). Metabolomics evaluation of serum markers for cachexia and their intra-day variation in patients with advanced pancreatic cancer. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0113259"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.urology.2006.09.039","article-title":"Interleukin 6 is associated with cachexia in patients with prostate cancer","volume":"69","author":"Kuroda","year":"2007","journal-title":"Urology"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1002\/jcsm.12121","article-title":"The Human Skeletal Muscle Proteome Project: A reappraisal of the current literature","volume":"8","author":"Semba","year":"2017","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"22001","DOI":"10.18632\/oncotarget.25146","article-title":"Proteomic profiling of skeletal and cardiac muscle in cancer cachexia: Alterations in sarcomeric and mitochondrial protein expression","volume":"9","author":"Shum","year":"2018","journal-title":"Oncotarget"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3059","DOI":"10.1038\/onc.2016.437","article-title":"Blockade of the IL-6 trans-signalling\/STAT3 axis suppresses cachexia in Kras-induced lung adenocarcinoma","volume":"36","author":"Miller","year":"2017","journal-title":"Oncogene"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"E410","DOI":"10.1152\/ajpendo.00039.2012","article-title":"JAK\/STAT3 pathway inhibition blocks skeletal muscle wasting downstream of IL-6 and in experimental cancer cachexia","volume":"303","author":"Bonetto","year":"2012","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1042\/bse0410173","article-title":"The ubiquitin-proteasome system and skeletal muscle wasting","volume":"41","author":"Attaix","year":"2005","journal-title":"Essays Biochem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1002\/jcsm.12232","article-title":"Mitochondrial degeneration precedes the development of muscle atrophy in progression of cancer cachexia in tumour-bearing mice","volume":"8","author":"Brown","year":"2017","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1016\/j.clnu.2007.03.011","article-title":"Pathophysiology of cancer cachexia: Much more than host-tumour interaction?","volume":"26","author":"Skipworth","year":"2007","journal-title":"Clin. Nutr."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1038\/nri.2016.150","article-title":"Regulation of muscle growth and regeneration by the immune system","volume":"17","author":"Tidball","year":"2017","journal-title":"Nat. Rev. Immunol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1083\/jcb.200105110","article-title":"A nitric oxide synthase transgene ameliorates muscular dystrophy in mdx mice","volume":"155","author":"Wehling","year":"2001","journal-title":"J. Cell. Biol."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Castiglioni, A., Corna, G., Rigamonti, E., Basso, V., Vezzoli, M., Monno, A., Almada, A.E., Mondino, A., Wagers, A.J., and Manfredi, A.A. (2015). FOXP3+ T Cells Recruited to Sites of Sterile Skeletal Muscle Injury Regulate the Fate of Satellite Cells and Guide Effective Tissue Regeneration. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0128094"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1038\/cdd.2015.171","article-title":"Cell death, clearance and immunity in the skeletal muscle","volume":"23","author":"Sciorati","year":"2016","journal-title":"Cell Death Differ."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1097\/SPC.0b013e3283311d09","article-title":"The role of cytokines in cancer cachexia","volume":"3","author":"Argiles","year":"2009","journal-title":"Curr. Opin. Support. Palliat. Care"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1177\/1076029618779133","article-title":"Preoperative Biomarker Panel, Including Fibrinogen and FVIII, Improves Diagnostic Accuracy for Pancreatic Ductal Adenocarcinoma","volume":"24","author":"Mattila","year":"2018","journal-title":"Clin. Appl. Thromb. Hemost."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1111\/jth.13612","article-title":"Increased thrombin generation in a mouse model of cancer cachexia is partially interleukin-6 dependent","volume":"15","author":"Reddel","year":"2017","journal-title":"J. Thromb. Haemost."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1002\/jcsm.12033","article-title":"Plasma growth differentiation factor 15 is associated with weight loss and mortality in cancer patients","volume":"6","author":"Lerner","year":"2015","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1038\/bjc.2016.3","article-title":"Identification of neutrophil-derived proteases and angiotensin II as biomarkers of cancer cachexia","volume":"114","author":"Penafuerte","year":"2016","journal-title":"Br. J. Cancer"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1097\/SPC.0000000000000091","article-title":"Role of interleukin-6 in cachexia: Therapeutic implications","volume":"8","author":"Narsale","year":"2014","journal-title":"Curr. Opin. Support. Palliat. Care"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/S0161-5890(02)00210-9","article-title":"The two faces of IL-6 on Th1\/Th2 differentiation","volume":"39","author":"Diehl","year":"2002","journal-title":"Mol. Immunol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1097\/JES.0b013e3181f44f11","article-title":"Interleukin 6 as a key regulator of muscle mass during cachexia","volume":"38","author":"Carson","year":"2010","journal-title":"Exerc. Sport Sci. Rev."},{"key":"ref_77","first-page":"3","article-title":"Age, Obesity, Sarcopenia, and Proximity to Death Explain Reduced Mean Muscle Attenuation in Patients with Advanced Cancer","volume":"3","author":"Esfandiari","year":"2014","journal-title":"J. Frailty Aging"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1186\/1477-7819-8-85","article-title":"The relationship among acute-phase response proteins, cytokines and hormones in cachectic patients with colon cancer","volume":"8","author":"Kemik","year":"2010","journal-title":"World J. Surg. Oncol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"323","DOI":"10.4062\/biomolther.2013.072","article-title":"Targeting the Transforming Growth Factor-beta Signaling in Cancer Therapy","volume":"21","author":"Sheen","year":"2013","journal-title":"Biomol. Ther."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1161\/CIRCHEARTFAILURE.114.001958","article-title":"Wnt\/beta-Catenin Signaling Contributes to Skeletal Myopathy in Heart Failure via Direct Interaction with Forkhead Box O","volume":"8","author":"Okada","year":"2015","journal-title":"Circ. Heart Fail."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1177\/002215549904700104","article-title":"Fibroblast growth factor promotes recruitment of skeletal muscle satellite cells in young and old rats","volume":"47","author":"Seger","year":"1999","journal-title":"J. Histochem. Cytochem."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1152\/japplphysiol.01305.2006","article-title":"Estradiol replacement reverses ovariectomy-induced muscle contractile and myosin dysfunction in mature female mice","volume":"102","author":"Moran","year":"2007","journal-title":"J. Appl. Physiol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1038\/bjc.2017.190","article-title":"Evaluation of serum microRNA biomarkers for gastric cancer based on blood and tissue pools profiling: The importance of miR-21 and miR-331","volume":"117","author":"Sierzega","year":"2017","journal-title":"Br. J. Cancer"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"506","DOI":"10.4161\/rna.8.3.14994","article-title":"Stable serum miRNA profiles as potential tool for non-invasive lung cancer diagnosis","volume":"8","author":"Keller","year":"2011","journal-title":"RNA Biol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1016\/S1470-2045(08)70153-0","article-title":"Prevalence and clinical implications of sarcopenic obesity in patients with solid tumours of the respiratory and gastrointestinal tracts: A population-based study","volume":"9","author":"Prado","year":"2008","journal-title":"Lancet Oncol."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/12\/12\/3787\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:45:34Z","timestamp":1760179534000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/12\/12\/3787"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,15]]},"references-count":85,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["cancers12123787"],"URL":"https:\/\/doi.org\/10.3390\/cancers12123787","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,15]]}}}