Identification of key genes associated with the effect of estrogen on ovarian cancer using microarray analysis.
OBJECTIVE
To identify key genes related to the effect of estrogen on ovarian cancer.


METHODS
Microarray data (GSE22600) were downloaded from Gene Expression Omnibus. Eight estrogen and seven placebo treatment samples were obtained using a 2 × 2 factorial designs, which contained 2 cell lines (PEO4 and 2008) and 2 treatments (estrogen and placebo). Differentially expressed genes were identified by Bayesian methods, and the genes with P < 0.05 and |log2FC (fold change)| ≥0.5 were chosen as cut-off criterion. Differentially co-expressed genes (DCGs) and differentially regulated genes (DRGs) were, respectively, identified by DCe function and DRsort function in DCGL package. Topological structure analysis was performed on the important transcriptional factors (TFs) and genes in transcriptional regulatory network using tYNA. Functional enrichment analysis was, respectively, performed for DEGs and the important genes using Gene Ontology and KEGG databases.


RESULTS
In total, 465 DEGs were identified. Functional enrichment analysis of DEGs indicated that ACVR2B, LTBP1, BMP7 and MYC involved in TGF-beta signaling pathway. The 2285 DCG pairs and 357 DRGs were identified. Topological structure analysis showed that 52 important TFs and 65 important genes were identified. Functional enrichment analysis of the important genes showed that TP53 and MLH1 participated in DNA damage response and the genes (ACVR2B, LTBP1, BMP7 and MYC) involved in TGF-beta signaling pathway.


CONCLUSIONS
TP53, MLH1, ACVR2B, LTBP1 and BMP7 might participate in the pathogenesis of ovarian cancer.
Key Laboratory for Molecular Enzymology and Engineering, The Ministry of Education, Jilin University, Changchun, 130012, China.
Shi-tao
ST
Zhang
Department of Anesthesiology, The Fifth Affiliated Hospital of Zunyi Medical College, Zhu Hai, 519100, China.
Chao
C
Zuo
Key Laboratory for Molecular Enzymology and Engineering, The Ministry of Education, Jilin University, Changchun, 130012, China.
Wan-nan
WN
Li
Key Laboratory for Molecular Enzymology and Engineering, The Ministry of Education, Jilin University, Changchun, 130012, China.
Xue-qi
XQ
Fu
Key Laboratory for Molecular Enzymology and Engineering, The Ministry of Education, Jilin University, Changchun, 130012, China.
Shu
S
Xing
Department of Obstetrics and Gynecology, China-Japan Union Hospital of Jilin University, 126 Xiantai Street, Changchun, 130033, China. xiaopingzhangxpz@163.com.
Xiao-ping
XP
Zhang
D001499:Bayes Theorem; D019295:Computational Biology; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D006801:Humans; D046228:Microarray Analysis / Q000379:methods*; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics*; D016212:Transforming Growth Factor beta
D004967:Estrogens; D014157:Transcription Factors; D016212:Transforming Growth Factor beta
Function enrichment; Ovarian cancer; Topological structure analysis; Transcriptional regulatory network analysis