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Published on: February 21, 2014
Identification of key genes associated with the effect of estrogen on ovarian cancer using microarray analysis
Shi-tao Zhang1, Chao Zuo2, Wan-nan Li1
1Key Laboratory for Molecular Enzymology and Engineering, The Ministry of Education, Jilin University, Changchun, 130012, China.
Purpose:
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.
Conclusion:
TP53, MLH1, ACVR2B, LTBP1 and BMP7 might participate in the pathogenesis of ovarian cancer.
Insights
Estrogen influences ovarian cancer development. Key genes like TP53, MLH1, ACVR2B, LTBP1, and BMP7 are implicated in its pathogenesis, particularly through DNA damage response and TGF-beta signaling pathways.
Area of Science:
- Genomics
- Oncology
- Molecular Biology
Background:
- Estrogen plays a significant role in the development and progression of ovarian cancer.
- Identifying molecular mechanisms underlying estrogen's effect is crucial for targeted therapies.
Purpose of the Study:
- To identify key genes and pathways affected by estrogen in ovarian cancer.
- To elucidate the molecular underpinnings of estrogen's influence on ovarian cancer pathogenesis.
Main Methods:
- Utilized microarray data (GSE22600) from estrogen and placebo-treated ovarian cancer cell lines.
- Employed Bayesian methods for identifying differentially expressed genes (DEGs) and differential co-expression (DCG) and regulation (DRG) analyses.
- Performed topological structure analysis of transcriptional regulatory networks and functional enrichment analysis (Gene Ontology, KEGG).
Main Results:
- Identified 465 DEGs, with ACVR2B, LTBP1, BMP7, and MYC involved in the TGF-beta signaling pathway.
- Discovered 2285 DCG pairs and 357 DRGs.
- Highlighted TP53 and MLH1 in DNA damage response, and ACVR2B, LTBP1, BMP7, MYC in TGF-beta signaling.
Conclusions:
- TP53, MLH1, ACVR2B, LTBP1, and BMP7 are potentially key players in ovarian cancer pathogenesis.
- These genes may mediate estrogen's effects through DNA damage response and TGF-beta signaling pathways.
- Findings provide insights into molecular targets for ovarian cancer treatment.
