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dc.contributor.authorHsu, Min-Kungen_US
dc.contributor.authorWu, I-Chingen_US
dc.contributor.authorCheng, Ching-Chiaen_US
dc.contributor.authorSu, Jen-Liangen_US
dc.contributor.authorHsieh, Chang-Huainen_US
dc.contributor.authorLin, Yeong-Shinen_US
dc.contributor.authorChen, Feng-Chien_US
dc.date.accessioned2015-12-02T02:59:40Z-
dc.date.available2015-12-02T02:59:40Z-
dc.date.issued2015-10-06en_US
dc.identifier.issn1949-2553en_US
dc.identifier.urihttp://dx.doi.org/10.18632/oncotarget.4810en_US
dc.identifier.urihttp://hdl.handle.net/11536/128419-
dc.description.abstractLung adenocarcinoma is one of the most deadly human diseases. However, the molecular mechanisms underlying this disease, particularly RNA splicing, have remained underexplored. Here, we report a triple-level (gene-, transcript-, and exon-level) analysis of lung adenocarcinoma transcriptomes from 77 paired tumor and normal tissues, as well as an analysis pipeline to overcome genetic variability for accurate differentiation between tumor and normal tissues. We report three major results. First, more than 5,000 differentially expressed transcripts/exonic regions occur repeatedly in lung adenocarcinoma patients. These transcripts/exonic regions are enriched in nicotine metabolism and ribosomal functions in addition to the pathways enriched for differentially expressed genes (cell cycle, extracellular matrix receptor interaction, and axon guidance). Second, classification models based on rationally selected transcripts or exonic regions can reach accuracies of 0.93 to 1.00 in differentiating tumor from normal tissues. Of the 28 selected exonic regions, 26 regions correspond to alternative exons located in such regulators as tumor suppressor (GDF10), signal receptor (LYVE1), vascular-specific regulator (RASIP1), ubiquitination mediator (RNF5), and transcriptional repressor (TRIM27). Third, classification systems based on 13 to 14 differentially expressed genes yield accuracies near 100%. Genes selected by both detection methods include C16orf59, DAP3, ETV4, GABARAPL1, PPAR, RADIL, RSPO1, SERTM1, SRPK1, ST6GALNAC6, and TNXB. Our findings imply a multilayered lung adenocarcinoma regulome in which transcript-/exon-level regulation may be dissociated from gene-level regulation. Our described method may be used to identify potentially important genes/transcripts/exonic regions for the tumorigenesis of lung adenocarcinoma and to construct accurate tumor vs. normal classification systems for this disease.en_US
dc.language.isoen_USen_US
dc.subjectlung adenocarcinomaen_US
dc.subjecttranscriptome analysisen_US
dc.subjectalternative splicingen_US
dc.subjectdifferential expressionen_US
dc.subjecttranscript-specific regulationen_US
dc.titleTriple-layer dissection of the lung adenocarcinoma transcriptome - regulation at the gene, transcript, and exon levelsen_US
dc.typeArticleen_US
dc.identifier.doi10.18632/oncotarget.4810en_US
dc.identifier.journalONCOTARGETen_US
dc.citation.issue30en_US
dc.citation.spage28755en_US
dc.citation.epage28773en_US
dc.contributor.department生物科技學系zh_TW
dc.contributor.departmentDepartment of Biological Science and Technologyen_US
dc.identifier.wosnumberWOS:000363183200028en_US
dc.citation.woscount0en_US
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