Multi-Omics Analysis Reveals a HIF Network and Hub Gene EPAS1 Associated with Lung Adenocarcinoma.

2.50
Hdl Handle:
http://hdl.handle.net/10146/618236
Title:
Multi-Omics Analysis Reveals a HIF Network and Hub Gene EPAS1 Associated with Lung Adenocarcinoma.
Authors:
Wang, Zhaoxi; Wei, Yongyue; Zhang, Ruyang; Su, Li; Gogarten, Stephanie M; Liu, Geoffrey; Brennan, Paul; Field, John K; McKay, James D; Lissowska, Jolanta; Swiatkowska, Beata; Janout, Vladimir; Bolca, Ciprian; Kontic, Milica; Scelo, Ghislaine; Zaridze, David; Laurie, Cathy C; Doheny, Kimberly F; Pugh, Elizabeth K; Marosy, Beth A; Hetrick, Kurt N; Xiao, Xiangjun; Pikielny, Claudio; Hung, Rayjean J; Amos, Christopher I; Lin, Xihong; Christiani, David C
Abstract:
Recent 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.
Affiliation:
Nofer Institute of Occupational Medicine
Citation:
EBioMedicine 2018, 32:93-101
Journal:
EBioMedicine
Issue Date:
Jun-2018
URI:
http://hdl.handle.net/10146/618236
DOI:
10.1016/j.ebiom.2018.05.024
PubMed ID:
29859855
Additional Links:
https://www.sciencedirect.com/science/article/pii/S2352396418301889?via%3Dihub
Type:
Article
Language:
en
ISSN:
2352-3964
Sponsors:
This 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.
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Full metadata record

DC FieldValue Language
dc.contributor.authorWang, Zhaoxien
dc.contributor.authorWei, Yongyueen
dc.contributor.authorZhang, Ruyangen
dc.contributor.authorSu, Lien
dc.contributor.authorGogarten, Stephanie Men
dc.contributor.authorLiu, Geoffreyen
dc.contributor.authorBrennan, Paulen
dc.contributor.authorField, John Ken
dc.contributor.authorMcKay, James Den
dc.contributor.authorLissowska, Jolantaen
dc.contributor.authorSwiatkowska, Beataen
dc.contributor.authorJanout, Vladimiren
dc.contributor.authorBolca, Ciprianen
dc.contributor.authorKontic, Milicaen
dc.contributor.authorScelo, Ghislaineen
dc.contributor.authorZaridze, Daviden
dc.contributor.authorLaurie, Cathy Cen
dc.contributor.authorDoheny, Kimberly Fen
dc.contributor.authorPugh, Elizabeth Ken
dc.contributor.authorMarosy, Beth Aen
dc.contributor.authorHetrick, Kurt Nen
dc.contributor.authorXiao, Xiangjunen
dc.contributor.authorPikielny, Claudioen
dc.contributor.authorHung, Rayjean Jen
dc.contributor.authorAmos, Christopher Ien
dc.contributor.authorLin, Xihongen
dc.contributor.authorChristiani, David Cen
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.en
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
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