TY - JOUR
T1 - Meta-analysis of microarray and RNA-Seq gene expression datasets for carcinogenic risk
T2 - An assessment of Bisphenol A
AU - Jung, Junghyun
AU - Mok, Changsoo
AU - Lee, Woosuk
AU - Jang, Wonhee
N1 - Publisher Copyright:
© 2017, The Korean Society of Toxicogenomics and Toxicoproteomics and Springer Science+Business Media B.V.
PY - 2017/6/1
Y1 - 2017/6/1
N2 - Bisphenol A (BPA) is an endocrine-disrupting chemical that is related to many diseases, including heart attacks and diabetes. Recently, several studies have reported the carcinogenic potential of BPA in rodents, yet carcinogenic effects of BPA in humans remains unclear. In this study, meta-analysis was applied to independent GEO datasets, based on 158 Affymetrix microarrays and 8 Illumina RNA-Seqs. Additionally, we performed functional enrichment analysis, disease similarity analysis based on Disease Ontology (DO) analysis, and network analysis. 1,993 (1,457 up-, 536 down-regulated) differentially expressed genes (DEGs) were identified from five GEO datasets by adjusting for batch effects. Using disease similarity analysis, we demonstrated that results of DO analysis of the top 20 diseases were highly related to breast cancer. Moreover, we showed that the DEGs were significantly enriched in gene expression datasets on human breast cancer tissue via gene set enrichment analysis. By performing network analysis, we finally identified 85 (68 up- and 17 down-regulated) DEGs, and some of their expression levels were validated by quantitative PCR. The identified DEGs were regarded as genetic markers for carcinogenic risks, indicating that BPA may be a potential carcinogenic chemical contributing to the cause of breast cancer in humans.
AB - Bisphenol A (BPA) is an endocrine-disrupting chemical that is related to many diseases, including heart attacks and diabetes. Recently, several studies have reported the carcinogenic potential of BPA in rodents, yet carcinogenic effects of BPA in humans remains unclear. In this study, meta-analysis was applied to independent GEO datasets, based on 158 Affymetrix microarrays and 8 Illumina RNA-Seqs. Additionally, we performed functional enrichment analysis, disease similarity analysis based on Disease Ontology (DO) analysis, and network analysis. 1,993 (1,457 up-, 536 down-regulated) differentially expressed genes (DEGs) were identified from five GEO datasets by adjusting for batch effects. Using disease similarity analysis, we demonstrated that results of DO analysis of the top 20 diseases were highly related to breast cancer. Moreover, we showed that the DEGs were significantly enriched in gene expression datasets on human breast cancer tissue via gene set enrichment analysis. By performing network analysis, we finally identified 85 (68 up- and 17 down-regulated) DEGs, and some of their expression levels were validated by quantitative PCR. The identified DEGs were regarded as genetic markers for carcinogenic risks, indicating that BPA may be a potential carcinogenic chemical contributing to the cause of breast cancer in humans.
KW - Bisphenol A
KW - Carcinogenic risks assessment
KW - Meta-analysis
KW - Network analysis
KW - Toxicogenomics
UR - http://www.scopus.com/inward/record.url?scp=85021287897&partnerID=8YFLogxK
U2 - 10.1007/s13273-017-0026-5
DO - 10.1007/s13273-017-0026-5
M3 - Article
AN - SCOPUS:85021287897
SN - 1738-642X
VL - 13
SP - 239
EP - 249
JO - Molecular and Cellular Toxicology
JF - Molecular and Cellular Toxicology
IS - 2
ER -