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Oncotarget. 2016 Aug 23;7(34):55249-55263. doi: 10.18632/oncotarget.10509.

Meta-dimensional data integration identifies critical pathways for susceptibility, tumorigenesis and progression of endometrial cancer.

Author information

1
Molecular Biosciences and Bioengineering Graduate Program, University of Hawaii at Manoa, Honolulu, HI, USA.
2
Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA.
3
Harvard School of Public Health, Harvard University, Boston, MA, USA.
4
Yale School of Public Health, Yale University, New Haven, CT, USA.
5
Institute for Biomedical Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
6
Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Abstract

Endometrial Cancer (EC) is one of the most common female cancers. Genome-wide association studies (GWAS) have been investigated to identify genetic polymorphisms that are predictive of EC risks. Here we utilized a meta-dimensional integrative approach to seek genetically susceptible pathways that may be associated with tumorigenesis and progression of EC. We analyzed GWAS data obtained from Connecticut Endometrial Cancer Study (CECS) and identified the top 20 EC susceptible pathways. To further verify the significance of top 20 EC susceptible pathways, we conducted pathway-level multi-omics analyses using EC exome-Seq, RNA-Seq and survival data, all based on The Cancer Genome Atlas (TCGA) samples. We measured the overall consistent rankings of these pathways in all four data types. Some well-studied pathways, such as p53 signaling and cell cycle pathways, show consistently high rankings across different analyses. Additionally, other cell signaling pathways (e.g. IGF-1/mTOR, rac-1 and IL-5 pathway), genetic information processing pathway (e.g. homologous recombination) and metabolism pathway (e.g. sphingolipid metabolism) are also highly associated with EC risks, diagnosis and prognosis. In conclusion, the meta-dimensional integration of EC cohorts has suggested some common pathways that may be associated from predisposition, tumorigenesis to progression.

KEYWORDS:

GWAS; data integration; data mining; endometrial cancer (EC); pathways

PMID:
27409342
PMCID:
PMC5342415
DOI:
10.18632/oncotarget.10509
[Indexed for MEDLINE]
Free PMC Article

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