Abstract
BackgroundOvarian cancer is the second fatal malignancy of the female reproductive system. Based on the cancer stem cell (CSC) theory, its poor prognosis of ovarian cancer attributed to tumor recurrence caused by CSCs. A variety of cell surface-specific markers have been employed to identify ovarian cancer stem cells (OCSCs). In this study, we attempted to explore the common feature in ovarian cancer stem cells sorted by multiple approaches.MethodsWe collected the gene expression profiles of OCSCs were from 5 public cohorts and employed R software and Bioconductor packages to establish differently expressed genes (DEGs) between OCSCs and parental cells. We extracted the integrated DEGs by protein-protein interaction (PPI) network construction and explored potential treatment by the Cellminer database.ResultsWe identified and integrated the DEGs of OCSCs sorted by multiple isolation approaches. Besides, we identified OCSCs share characteristics in the lipid metabolism and extracellular matrix changes. Moreover, we obtained 16 co-expressed core genes, such as FOXQ1, MMP7, AQP5, RBM47, ETV4, NPW, SUSD2, SFRP2, IDO1, ANPEP, CXCR4, SCNN1A, SPP1 and IFI27 (upregulated) and SERPINE1, DUSP1, CD40, and IL6 (downregulated). Through correlation analysis, we screened out ten potential drugs to target the core genes.ConclusionBased on the comprehensive analysis of the genomic datasets with different sorting methods of OCSCs, we figured out the common driving genes to regulating OCSC and obtained ten new potential therapies for eliminating ovarian cancer stem cells. Hence, the findings of our study might have potential clinical significance.
Highlights
Ovarian cancer is the second fatal malignancy of the female reproductive system
Combined with WGCNA and protein-protein interaction (PPI) network, we identified the hub genes of ovarian cancer stem cells (OCSCs) and obtained 16 coexpressed core genes, such as FOXQ1, MMP7, AQP5, RBM47, ETV4, NPW, SUSD2, SFRP2, IDO1, ANPEP, CXCR4, SCNN1A, SPP1 and IFI27 and SERPINE1, DUSP1, CD40, and IL6
Flow chart for the study design In this study, we conducted a comprehensive analysis of common essential genes in OCSCs isolated by deferent methods and their critical roles in OV by several computational methods
Summary
Based on the cancer stem cell (CSC) theory, its poor prognosis of ovarian cancer attributed to tumor recurrence caused by CSCs. A variety of cell surface-specific markers have been employed to identify ovarian cancer stem cells (OCSCs). We attempted to explore the common feature in ovarian cancer stem cells sorted by multiple approaches. Several studies have contributed to the isolation and identification of OCSCs. Spheroids’ formation in cancer stem cell culture has been recognized as the first commonly used approach [5, 6]. Based on cell surface markers, CD44, CD117, and CD133 etc., OCSCs have been successfully identified and isolated [9,10,11]. Cells expressing high levels of ALDH1 can be identified by ALDEFLUOR assay and isolated by the ALDH1 antibody [10, 12, 13]
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