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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 93-101 |
| Number of pages | 9 |
| Journal | EBioMedicine |
| Volume | 32 |
| DOIs | |
| State | Published - Jun 1 2018 |
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Keywords
- Hypoxia-inducible factor
- Integrated analysis
- Lung adenocarcinoma
- Network analysis
- Non-small cell lung cancer
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
Cite this
Multi-Omics Analysis Reveals a HIF Network and Hub Gene EPAS1 Associated with Lung Adenocarcinoma. / 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; Pugh, Elizabeth; Marosy, Beth A.; Hetrick, Kurt N.; Xiao, Xiangjun; Pikielny, Claudio; Hung, Rayjean J.; Amos, Christopher I.; Lin, Xihong; Christiani, David C.
In: EBioMedicine, Vol. 32, 01.06.2018, p. 93-101.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Multi-Omics Analysis Reveals a HIF Network and Hub Gene EPAS1 Associated with Lung Adenocarcinoma
AU - Wang, Zhaoxi
AU - Wei, Yongyue
AU - Zhang, Ruyang
AU - Su, Li
AU - Gogarten, Stephanie M.
AU - Liu, Geoffrey
AU - Brennan, Paul
AU - Field, John K.
AU - McKay, James D.
AU - Lissowska, Jolanta
AU - Swiatkowska, Beata
AU - Janout, Vladimir
AU - Bolca, Ciprian
AU - Kontic, Milica
AU - Scelo, Ghislaine
AU - Zaridze, David
AU - Laurie, Cathy C.
AU - Doheny, Kimberly
AU - Pugh, Elizabeth
AU - Marosy, Beth A.
AU - Hetrick, Kurt N.
AU - Xiao, Xiangjun
AU - Pikielny, Claudio
AU - Hung, Rayjean J.
AU - Amos, Christopher I.
AU - Lin, Xihong
AU - Christiani, David C.
PY - 2018/6/1
Y1 - 2018/6/1
N2 - 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.
AB - 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.
KW - Hypoxia-inducible factor
KW - Integrated analysis
KW - Lung adenocarcinoma
KW - Network analysis
KW - Non-small cell lung cancer
UR - http://www.scopus.com/inward/record.url?scp=85047757715&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85047757715&partnerID=8YFLogxK
U2 - 10.1016/j.ebiom.2018.05.024
DO - 10.1016/j.ebiom.2018.05.024
M3 - Article
C2 - 29859855
AN - SCOPUS:85047757715
VL - 32
SP - 93
EP - 101
JO - EBioMedicine
JF - EBioMedicine
SN - 2352-3964
ER -