{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T21:20:10Z","timestamp":1792704010499,"version":"4.5.0"},"reference-count":62,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2019,12,11]],"date-time":"2019-12-11T00:00:00Z","timestamp":1576022400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","award":["92003564"],"award-info":[{"award-number":["92003564"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2020,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Cachexia, highly prevalent in patients with non\u2010small cell lung cancer (NSCLC), impairs quality of life and is associated with reduced tolerance and responsiveness to cancer therapy and decreased survival. MicroRNAs (miRNAs) are small non\u2010coding RNAs that play a central role in post\u2010transcriptional gene regulation. Changes in intramuscular levels of miRNAs have been implicated in muscle wasting conditions. Here, we aimed to identify miRNAs that are differentially expressed in skeletal muscle of cachectic lung cancer patients to increase our understanding of cachexia and to allow us to probe their potential as therapeutic targets.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A total of 754 unique miRNAs were profiled and analysed in vastus lateralis muscle biopsies of newly diagnosed treatment\u2010na\u00efve NSCLC patients with cachexia (<jats:italic>n<\/jats:italic> = 8) and age\u2010matched and sex\u2010matched healthy controls (<jats:italic>n<\/jats:italic> = 8). miRNA expression analysis was performed using a TaqMan MicroRNA Array. <jats:italic>In silico<\/jats:italic> network analysis was performed on all significant differentially expressed miRNAs. Differential expression of the top\u2010ranked miRNAs was confirmed using reverse transcription\u2013quantitative real\u2010time PCR in an extended group (<jats:italic>n<\/jats:italic> = 48) consisting of NSCLC patients with (<jats:italic>n<\/jats:italic> = 15) and without cachexia (<jats:italic>n<\/jats:italic> = 11) and healthy controls (<jats:italic>n<\/jats:italic> = 22). Finally, these miRNAs were subjected to univariate and multivariate Cox proportional hazard analysis using overall survival and treatment\u2010induced toxicity data obtained during the follow\u2010up of this group of patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified 28 significant differentially expressed miRNAs, of which five miRNAs were up\u2010regulated and 23 were down\u2010regulated. <jats:italic>In silico<\/jats:italic> miRNA\u2010target prediction analysis showed 158 functional gene targets, and pathway analysis identified 22 pathways related to the degenerative or regenerative processes of muscle tissue. Subsequently, the expression of six top\u2010ranked miRNAs was measured in muscle biopsies of the entire patient group. Five miRNAs were detectable with reverse transcription\u2013quantitative real\u2010time PCR analysis, and their altered expression (expressed as fold change, FC) was confirmed in muscle of cachectic NSCLC patients compared with healthy control subjects: miR\u2010424\u20105p (FC = 4.5), miR\u2010424\u20103p (FC = 12), miR\u2010450a\u20105p (FC = 8.6), miR\u2010144\u20105p (FC = 0.59), and miR\u2010451a (FC = 0.57). In non\u2010cachectic NSCLC patients, only miR\u2010424\u20103p was significantly increased (FC = 5.6) compared with control. Although the statistical support was not sufficient to imply these miRNAs as individual predictors of overall survival or treatment\u2010induced toxicity, when combined in multivariate analysis, miR\u2010450\u20105p and miR\u2010451a resulted in a significant stratification between short\u2010term and long\u2010term survival.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We identified differentially expressed miRNAs putatively involved in lung cancer cachexia. These findings call for further studies to investigate the causality of these miRNAs in muscle atrophy and the mechanisms underlying their differential expression in lung cancer cachexia.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.12512","type":"journal-article","created":{"date-parts":[[2019,12,12]],"date-time":"2019-12-12T06:24:41Z","timestamp":1576131881000},"page":"452-463","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Identification of microRNAs in skeletal muscle associated with lung cancer cachexia"],"prefix":"10.1002","volume":"11","author":[{"given":"Wouter R.P.H.","family":"van de Worp","sequence":"first","affiliation":[{"name":"Department of Respiratory Medicine, NUTRIM Maastricht University Medical Center+  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annemie M.W.J.","family":"Schols","sequence":"additional","affiliation":[{"name":"Department of 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