Preliminary Study Of Tumor Stem Cell Markers And Targeted Therapy With Tumor Stem Cell For Ovarian Cancer

Objective:1.A variety of cell surface markers and multiple approaches have been employed to identify ovarian cancer stem cells(OCSCs).Our study aimed to explore the common feature in ovarian cancer stem cells sorted by multiple approaches.2.CD90 has been recognized as a stem cell marker for various kinds of cancer,the mechanism of CD90 as a marker for OCSCs has not been clarified.The study aimed to explore the mechanism of CD90 as a marker for OCSCs.Methods:1.We collected the gene expression profiles of OCSCs were from 5 public cohorts and established 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.2.Analyses of public database and clinical specimen were performed to determine the expression level and clinical significance of CD90 in EOC.CD90 positive cells were sorted.The influence of CD90 expression on platinum resistance,metastasis and invasiveness was evaluated through a series of in vitro and in vivo experiments.Western blot analysis,Quantitative real-time PCR(q RT-PCR),Gene set enrichment analysis and integrative database analysis were carried out to investigate the underlying mechanism for CD90-mediated tumorigenesis in EOC.Results:1.We 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 sixteen co-expressed core genes,such as FOXQ1,MMP7,AQP5,RBM47,ETV4,NPW,SUSD2,SFRP2,IDO1,ANPEP,CXCR4,SCNN1 A,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.2.Here we report that CD90 is a CSCs surface marker and represents a subpopulation with high metastatic potential in epithelial ovarian cancer.Clinical data showed that a high frequency of CD90 is associated with poor prognosis.The CD90 highly expressed(CD90+)population in EOC cells harbors high stemness features and tumorigenicity.Migration and invasion assays identified CD90+ cells and CD90-transfected cells in ovarian cancer cells exhibited dramatically elevated invasiveness.Further experiments demonstrated that ITGA5/SRC/FAK pathway is one mechanism by which CD90+ cells hold enhanced metastatic phenotypes in ovarian cancer.Our work with an orthotopic ovarian cancer model also confirmed CD90 facilitate cancer cell in peritoneal cavity dissemination and dasatinib treatment partly blocked this process.Conclusion:1.Based 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.2.Collectively,our findings demonstrated CD90 could be a potential CSC marker in EOC,and targeting ITGA5/SRC/FAK pathway may be a novel therapeutic strategy for EOC with high CD90 expression.