{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T04:34:32Z","timestamp":1773981272638,"version":"3.50.1"},"reference-count":78,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2019,8,26]],"date-time":"2019-08-26T00:00:00Z","timestamp":1566777600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["17\/21223-9"],"award-info":[{"award-number":["17\/21223-9"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Cachexia is a syndrome characterized by an ongoing loss of skeletal muscle mass associated with poor patient prognosis in non-small cell lung cancer (NSCLC). However, prognostic cachexia biomarkers in NSCLC are unknown. Here, we analyzed computed tomography (CT) images and tumor transcriptome data to identify potentially secreted cachexia biomarkers (PSCB) in NSCLC patients with low-muscularity. We integrated radiomics features (pectoralis muscle, sternum, and tenth thoracic (T10) vertebra) from CT of 89 NSCLC patients, which allowed us to identify an index for screening muscularity. Next, a tumor transcriptomic-based secretome analysis from these patients (discovery set) was evaluated to identify potential cachexia biomarkers in patients with low-muscularity. The prognostic value of these biomarkers for predicting recurrence and survival outcome was confirmed using expression data from eight lung cancer datasets (validation set). Finally, C2C12 myoblasts differentiated into myotubes were used to evaluate the ability of the selected biomarker, interleukin (IL)-8, in inducing muscle cell atrophy. We identified 75 over-expressed transcripts in patients with low-muscularity, which included IL-6, CSF3, and IL-8. Also, we identified NCAM1, CNTN1, SCG2, CADM1, IL-8, NPTX1, and APOD as PSCB in the tumor secretome. These PSCB were capable of distinguishing worse and better prognosis (recurrence and survival) in NSCLC patients. IL-8 was confirmed as a predictor of worse prognosis in all validation sets. In vitro assays revealed that IL-8 promoted C2C12 myotube atrophy. Tumors from low-muscularity patients presented a set of upregulated genes encoding for secreted proteins, including pro-inflammatory cytokines that predict worse overall survival in NSCLC. Among these upregulated genes, IL-8 expression in NSCLC tissues was associated with worse prognosis, and the recombinant IL-8 was capable of triggering atrophy in C2C12 myotubes.<\/jats:p>","DOI":"10.3390\/cancers11091251","type":"journal-article","created":{"date-parts":[[2019,8,27]],"date-time":"2019-08-27T11:13:30Z","timestamp":1566904410000},"page":"1251","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Tumor Transcriptome Reveals High Expression of IL-8 in Non-Small Cell Lung Cancer Patients with Low Pectoralis Muscle Area and Reduced Survival"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4803-0933","authenticated-orcid":false,"given":"Sarah","family":"Santiloni Cury","sequence":"first","affiliation":[{"name":"Department of Morphology, Institute of Biosciences, S\u00e3o Paulo State University (UNESP), Botucatu 18618-689, S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diogo","family":"de Moraes","sequence":"additional","affiliation":[{"name":"Department of Morphology, Institute of Biosciences, S\u00e3o Paulo State University (UNESP), Botucatu 18618-689, S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0649-8279","authenticated-orcid":false,"given":"Paula","family":"Paccielli Freire","sequence":"additional","affiliation":[{"name":"Department of Morphology, Institute of Biosciences, S\u00e3o Paulo State University (UNESP), Botucatu 18618-689, S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Grasieli","family":"de Oliveira","sequence":"additional","affiliation":[{"name":"Department of Morphology, Institute of Biosciences, S\u00e3o Paulo State University (UNESP), Botucatu 18618-689, S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Douglas","family":"Ven\u00e2ncio Pereira Marques","sequence":"additional","affiliation":[{"name":"Department of Morphology, Institute of Biosciences, S\u00e3o Paulo State University (UNESP), Botucatu 18618-689, S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Geysson","family":"Javier Fernandez","sequence":"additional","affiliation":[{"name":"Department of Morphology, Institute of Biosciences, S\u00e3o Paulo State University (UNESP), Botucatu 18618-689, S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maeli","family":"Dal-Pai-Silva","sequence":"additional","affiliation":[{"name":"Department of Morphology, Institute of Biosciences, S\u00e3o Paulo State University (UNESP), Botucatu 18618-689, S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u00c9rica","family":"Nishida Hasimoto","sequence":"additional","affiliation":[{"name":"Department of Surgery and Orthopedics, Faculty of Medicine, S\u00e3o Paulo State University (UNESP), Botucatu 18618687, S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricia","family":"Pintor dos Reis","sequence":"additional","affiliation":[{"name":"Department of Surgery and Orthopedics, Faculty of Medicine, S\u00e3o Paulo State University (UNESP), Botucatu 18618687, S\u00e3o Paulo, Brazil"},{"name":"Experimental Research Unit, Faculty of Medicine, S\u00e3o Paulo State University (UNESP), Botucatu 18618687, S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"Regina Rogatto","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Vejle Hospital, Institute of Regional Health Research, University of Southern Denmark, Vejle 7100, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4901-7714","authenticated-orcid":false,"given":"Robson","family":"Francisco Carvalho","sequence":"additional","affiliation":[{"name":"Department of Morphology, Institute of Biosciences, S\u00e3o Paulo State University (UNESP), Botucatu 18618-689, S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,8,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1002\/ijc.29210","article-title":"Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012","volume":"136","author":"Ferlay","year":"2015","journal-title":"Int. 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