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dc.contributor.authorWang, Zhaoxi
dc.contributor.authorWei, Yongyue
dc.contributor.authorZhang, Ruyang
dc.contributor.authorSu, Li
dc.contributor.authorGogarten, Stephanie M
dc.contributor.authorLiu, Geoffrey
dc.contributor.authorBrennan, Paul
dc.contributor.authorField, John K
dc.contributor.authorMcKay, James D
dc.contributor.authorLissowska, Jolanta
dc.contributor.authorSwiatkowska, Beata
dc.contributor.authorJanout, Vladimir
dc.contributor.authorBolca, Ciprian
dc.contributor.authorKontic, Milica
dc.contributor.authorScelo, Ghislaine
dc.contributor.authorZaridze, David
dc.contributor.authorLaurie, Cathy C
dc.contributor.authorDoheny, Kimberly F
dc.contributor.authorPugh, Elizabeth K
dc.contributor.authorMarosy, Beth A
dc.contributor.authorHetrick, Kurt N
dc.contributor.authorXiao, Xiangjun
dc.contributor.authorPikielny, Claudio
dc.contributor.authorHung, Rayjean J
dc.contributor.authorAmos, Christopher I
dc.contributor.authorLin, Xihong
dc.contributor.authorChristiani, David C
dc.date.accessioned2018-12-04T09:59:38Z
dc.date.available2018-12-04T09:59:38Z
dc.date.issued2018-06
dc.identifier.citationEBioMedicine 2018, 32:93-101en
dc.identifier.issn2352-3964
dc.identifier.pmid29859855
dc.identifier.doi10.1016/j.ebiom.2018.05.024
dc.identifier.urihttp://hdl.handle.net/10146/618236
dc.description.abstractRecent technological advancements have permitted high-throughput measurement of the human genome, epigenome, metabolome, transcriptome, and proteome at the population level. We hypothesized that subsets of genes identified from omic studies might have closely related biological functions and thus might interact directly at the network level. Therefore, we conducted an integrative analysis of multi-omic datasets of non-small cell lung cancer (NSCLC) to search for association patterns beyond the genome and transcriptome. A large, complex, and robust gene network containing well-known lung cancer-related genes, including EGFR and TERT, was identified from combined gene lists for lung adenocarcinoma. Members of the hypoxia-inducible factor (HIF) gene family were at the center of this network. Subsequent sequencing of network hub genes within a subset of samples from the Transdisciplinary Research in Cancer of the Lung-International Lung Cancer Consortium (TRICL-ILCCO) consortium revealed a SNP (rs12614710) in EPAS1 associated with NSCLC that reached genome-wide significance (OR = 1.50; 95% CI: 1.31-1.72; p = 7.75 × 10-9). Using imputed data, we found that this SNP remained significant in the entire TRICL-ILCCO consortium (p = .03). Additional functional studies are warranted to better understand interrelationships among genetic polymorphisms, DNA methylation status, and EPAS1 expression.
dc.description.sponsorshipThis work was supported by the National Institutes of Health (NIH CA092824, CA090578, CA074386, and CA209414). Funding source for KFD, EWP, KNH, BAM (affiliation 7) is NIH contract HHSN268201200008I. The Toronto MSH-PMH study was supported by The Canadian Cancer Society Research Institute (020214), Ontario Institute of Cancer and Cancer Care Ontario Chair Award to R.J.H. and G.L. and the Alan Brown Chair and Lusi Wong Programs at the Princess Margaret Hospital Foundation. The data harmonization of the epidemiological variables across the studies is supported by National Institute of Health (U19-CA148127) and Lunenfeld-Tanenbaum Research Institute, Sinai Health System.en
dc.language.isoenen
dc.relation.urlhttps://www.sciencedirect.com/science/article/pii/S2352396418301889?via%3Dihuben
dc.rightsArchived with thanks to EBioMedicineen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectHypoxia-inducible factoren
dc.subjectIntegrated analysisen
dc.subjectLung adenocarcinomaen
dc.subjectNetwork analysisen
dc.subjectNon-small cell lung canceren
dc.subject.meshAdenocarcinoma
dc.subject.meshAged
dc.subject.meshBasic Helix-Loop-Helix Transcription Factors
dc.subject.meshCarcinoma, Non-Small-Cell Lung
dc.subject.meshDNA Methylation
dc.subject.meshFemale
dc.subject.meshGene Expression Regulation, Neoplastic
dc.subject.meshGenetic Association Studies
dc.subject.meshGenetic Predisposition to Disease
dc.subject.meshHumans
dc.subject.meshHypoxia-Inducible Factor 1, alpha Subunit
dc.subject.meshLung Neoplasms
dc.subject.meshMale
dc.subject.meshMiddle Aged
dc.subject.meshPolymorphism, Single Nucleotide
dc.titleMulti-Omics Analysis Reveals a HIF Network and Hub Gene EPAS1 Associated with Lung Adenocarcinoma.en
dc.typeArticleen
dc.contributor.departmentNofer Institute of Occupational Medicineen
dc.identifier.journalEBioMedicineen
refterms.dateFOA2018-12-17T18:11:45Z
html.description.abstractRecent technological advancements have permitted high-throughput measurement of the human genome, epigenome, metabolome, transcriptome, and proteome at the population level. We hypothesized that subsets of genes identified from omic studies might have closely related biological functions and thus might interact directly at the network level. Therefore, we conducted an integrative analysis of multi-omic datasets of non-small cell lung cancer (NSCLC) to search for association patterns beyond the genome and transcriptome. A large, complex, and robust gene network containing well-known lung cancer-related genes, including EGFR and TERT, was identified from combined gene lists for lung adenocarcinoma. Members of the hypoxia-inducible factor (HIF) gene family were at the center of this network. Subsequent sequencing of network hub genes within a subset of samples from the Transdisciplinary Research in Cancer of the Lung-International Lung Cancer Consortium (TRICL-ILCCO) consortium revealed a SNP (rs12614710) in EPAS1 associated with NSCLC that reached genome-wide significance (OR = 1.50; 95% CI: 1.31-1.72; p = 7.75 × 10-9). Using imputed data, we found that this SNP remained significant in the entire TRICL-ILCCO consortium (p = .03). Additional functional studies are warranted to better understand interrelationships among genetic polymorphisms, DNA methylation status, and EPAS1 expression.


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