Abstract
Background and aims: Ovarian cancer (OC) is the seventh most commonly detected cancer among women. This study aimed to map the hub and core genes and potential pathways that might be involved in the molecular pathogenesis of OC.Methods: In the present work, we analyzed a microarray dataset (GSE126519) from the Gene Expression Omnibus (GEO) database and used the GEO2R tool to screen OC cells and ovarian SINE-resistant cancer cells for differentially expressed genes (DEGs). For the functional annotation of the DEGs, we conducted Gene Ontology (GO) and pathway enrichment analyses (KEGG) using the DAVID v6.8 online server and GenoGo Metacore™, Cortellis Solution software. Protein–protein interaction (PPI) networks were constructed using the STRING database, and Cytoscape software was used for visualization. The survival analysis was performed using the online platform GEPIA2 to determine the prognostic value of the expression of hub genes in cell lines from OC patients.Results: We identified a total of 809 upregulated and 700 downregulated DEGs. GO analysis revealed that the genes with statistically significant differences in expression were mainly associated with biological processes involved in the cell cycle, the mitotic cell cycle, mitotic nuclear division, organ morphogenesis, cell development, and cell morphogenesis. By using the Analyze Networks (AN) algorithm in GeneGo, we identified the most relevant biological networks involving DEGs that were mainly enriched in the cell cycle (in metaphase checkpoints) and revealed the role of APC in cell cycle regulation pathways. We found 10 hub genes and four core genes (FZD6, FZD8, CDK2, and RBBP8) that are strongly linked to OC.Conclusion: This study sheds light on the molecular pathogenesis of OC and is expected to provide potential molecular biomarkers that are beneficial for the treatment and clinical molecular diagnosis of OC.
Highlights
Ovarian cancer (OC) is the seventh most frequently detected cancer among women worldwide (Reid et al, 2017)
A selective inhibitor of nuclear export (SINE) acts along with CMR1 to block its interaction with nuclear proteins intended to be exported to the cytoplasm; inhibitors of CMR1 are known as SINE compounds (Gerecitano, 2014)
The expression profiling was performed on the OC gene dataset GSE126519, which was retrieved from GEO (Gene Expression Omnibus database, https://www.ncbi.nlm.nih.gov/ geo/) and includes gene expression datasets from RNA-seq, highthroughput hybridization array, DNAseq, ChIPs, and microarray (Barrett et al, 2013)
Summary
Ovarian cancer (OC) is the seventh most frequently detected cancer among women worldwide (Reid et al, 2017). Epithelial cancers represent ∼90% of OC in patients with different ailments (Cancer Genome Atlas Research Network, 2011) comprising five distinct histological subtypes that have various distinguishable complications, sources of cells, molecular compositions, clinical signs, and symptoms and treatments (Matulonis et al, 2016). Recent work has revealed that SINE compounds enhance the proteasomal deterioration of CMR1, increase the nuclear retention of FOXO and p53, and contribute to enhanced apoptosis in prostate cancer cell lines (Mendonca et al, 2014). There is a need to understand the complete set of molecular mechanisms underlying SINE resistance in OC cell lines.
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