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Given this, the importance of research on its pathophysiology and therapy remains a key health issue. To assist in this endeavor, recent oncology studies are adopting Systems Biology approaches and bioinformatics to analyze and understand <jats:italic>omics<\/jats:italic> data, bringing new insights about this disease and its treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used reverse engineering of transcriptomic data to reconstruct nontumorous lung reference networks, focusing on transcription factors (TFs) and their inferred target genes, referred as regulatory units or regulons. Afterwards, we used 13 case\u2010control studies to identify TFs acting as master regulators of the disease and their regulatory units. Furthermore, the inferred activation patterns of regulons were used to evaluate patient <jats:italic>survival<\/jats:italic> and search drug candidates for repositioning.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The regulatory units under the influence of <jats:italic>ATOH8<\/jats:italic>, <jats:italic>DACH1<\/jats:italic>, <jats:italic>EPAS1<\/jats:italic>, <jats:italic>ETV5<\/jats:italic>, <jats:italic>FOXA2<\/jats:italic>, <jats:italic>FOXM1<\/jats:italic>, <jats:italic>HOXA4<\/jats:italic>, <jats:italic>SMAD6<\/jats:italic>, and <jats:italic>UHRF1<\/jats:italic> transcription factors were consistently associated with the pathological phenotype, suggesting that they may be master regulators of lung adenocarcinoma. We also observed that the inferred activity of <jats:italic>FOXA2<\/jats:italic>, <jats:italic>FOXM1<\/jats:italic>, and <jats:italic>UHRF1<\/jats:italic> was significantly associated with risk of death in patients. Finally, we obtained deptropine, promazine, valproic acid, azacyclonol, methotrexate, and ChemBridge ID compound 5109870 as potential candidates to revert the molecular profile leading to decreased survival.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Using an integrated transcriptomics approach, we identified master regulator candidates involved with the development and prognostic of lung adenocarcinoma, as well as potential drugs for repurposing.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.2493","type":"journal-article","created":{"date-parts":[[2019,9,10]],"date-time":"2019-09-10T13:39:17Z","timestamp":1568122757000},"page":"6717-6729","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Integrated transcriptomics reveals master regulators of lung adenocarcinoma and novel repositioning of drug candidates"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3924-5278","authenticated-orcid":false,"given":"Marco Ant\u00f4nio","family":"De Bastiani","sequence":"first","affiliation":[{"name":"Laboratory of Cellular Biochemistry Department of Biochemistry Federal University of Rio Grande do Sul (UFRGS) Porto Alegre RS Brazil"},{"name":"National Institute of Science and Technology for Translational Medicine (INCT\u2010TM) Porto Alegre RS Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9152-4229","authenticated-orcid":false,"given":"F\u00e1bio","family":"Klamt","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Biochemistry Department of Biochemistry Federal University of Rio Grande do Sul (UFRGS) Porto Alegre RS Brazil"},{"name":"National Institute of Science and Technology for Translational Medicine (INCT\u2010TM) Porto Alegre RS Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,9,10]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21492"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra0802714"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00595-013-0636-z"},{"key":"e_1_2_8_5_1","volume-title":"Cancer, Lung Adenocarcinoma","author":"Bhimji SS","year":"2018"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.15.0375"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2918"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt376"},{"key":"e_1_2_8_9_1","first-page":"346","article-title":"Data\u2010 and knowledge\u2010based modeling of gene regulatory networks: an update","volume":"14","author":"Linde J","year":"2015","journal-title":"EXCLI J"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.4172\/2157-7633.1000e114"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.cco.0000432528.88101.1a"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trecan.2015.07.001"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.4155\/fmc.14.66"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ddtec.2015.06.004"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/7147039"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0086299"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2044"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv007"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms3464"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3458"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-7-S1-S7"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature08712"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0506580102"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/biomet\/81.3.515"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-14-7"},{"key":"e_1_2_8_26_1","volume-title":"R Packag version 03","author":"Kassambara A","year":"2017"},{"key":"e_1_2_8_27_1","volume-title":"R Top Doc","author":"Therneau TM","year":"2015"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1132939"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2018.00697"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btv723"},{"key":"e_1_2_8_31_1","unstructured":"R Core Team.R: A Language and Environment for Statistical Computing.Vienna Austria:R Foundation for Statistical Computing;2019.https:\/\/www.R-project.org\/. 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