{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T19:21:21Z","timestamp":1790018481762,"version":"4.0.1"},"reference-count":65,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,10,6]],"date-time":"2017-10-06T00:00:00Z","timestamp":1507248000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2018,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Alternative splicing (AS) is a post\u2010transcriptional gene regulatory mechanism that contributes to proteome diversity. Aberrant splicing mechanisms contribute to various cancers and muscle\u2010related conditions such as Duchenne muscular dystrophy. However, dysregulation of AS in cancer cachexia (CC) remains unexplored. Our objectives were (i) to profile alternatively spliced genes (ASGs) on a genome\u2010wide scale and (ii) to identify differentially expressed alternatively spliced genes (DASGs) associated with CC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Rectus abdominis muscle biopsies obtained from cancer patients were stratified into cachectic cases (<jats:italic>n<\/jats:italic>\u00a0=\u00a021, classified based on International consensus diagnostic framework for CC) and non\u2010cachectic controls (<jats:italic>n<\/jats:italic>\u00a0=\u00a019, weight stable cancer patients). Human transcriptome array 2.0 was used for profiling ASGs using the total RNA isolated from muscle biopsies. Representative DASG signatures were validated using semi\u2010quantitative RT\u2013PCR.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified 8960 ASGs, of which 922 DASGs (772 up\u2010regulated and 150 down\u2010regulated) were identified at \u22651.4 fold\u2010change and <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05. Representative DASGs validated by semi\u2010quantitative RT\u2013PCR confirmed the primary findings from the human transcriptome arrays. Identified DASGs were associated with myogenesis, adipogenesis, protein ubiquitination, and inflammation. Up to 10% of the DASGs exhibited cassette exon (exon included or skipped) as a predominant form of AS event. We also observed other forms of AS events such as intron retention, alternate promoters.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Overall, we have, for the first time, conducted global profiling of muscle tissue to identify DASGs associated with CC. The mechanistic roles of the identified DASGs in CC pathophysiology using model systems is warranted, as well as replication of findings in independent cohorts.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.12235","type":"journal-article","created":{"date-parts":[[2017,10,6]],"date-time":"2017-10-06T05:22:40Z","timestamp":1507267360000},"page":"60-70","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Differentially expressed alternatively spliced genes in skeletal muscle from cancer patients with cachexia"],"prefix":"10.1002","volume":"9","author":[{"given":"Ashok","family":"Narasimhan","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine and Pathology University of Alberta  Edmonton AB T6G 1Z2 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russell","family":"Greiner","sequence":"additional","affiliation":[{"name":"Department of Computing Sciences University of Alberta  Edmonton AB T6G 2E8 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver F.","family":"Bathe","sequence":"additional","affiliation":[{"name":"Departments of Surgery and Oncology University of Calgary  Calgary AB T2N 1N4 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vickie","family":"Baracos","sequence":"additional","affiliation":[{"name":"Department of Oncology University of Alberta  Edmonton AB T6G 1Z2 Canada"},{"name":"Cross Cancer Institute  Edmonton AB T6G 1Z2 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sambasivarao","family":"Damaraju","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology University of Alberta  Edmonton AB T6G 1Z2 Canada"},{"name":"Cross Cancer Institute  Edmonton AB T6G 1Z2 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,10,6]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3525"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.9.12.1288"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2776"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.264"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2011.03.006"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj3050373"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.surg.2011.05.011"},{"key":"e_1_2_7_9_1","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1101\/gad.1048803","article-title":"Pre\u2010mRNA splicing and human disease","volume":"4","author":"Faustino NA","year":"2003","journal-title":"Genes Dev"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.2649"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.4161\/rna.7.4.12258"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(10)70218-7"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1177\/0148607188012003286"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clnu.2007.03.011"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-med-061509-131248"},{"key":"e_1_2_7_16_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pone.0013604","article-title":"Muscle wasting and impaired myogenesis in tumor bearing mice are prevented by ERK inhibition","volume":"5","author":"Penna F","year":"2010","journal-title":"PLoS One"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq614"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2013.12.029"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-2952(01)00785-7"},{"key":"e_1_2_7_20_1","unstructured":"EswaranJ HorvathA GodboleS ReddySD MudvariP OhshiroKet al.RNA sequencing of cancer reveals novel splicing alterations. 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