Deciphering the dynamic changes of immune cells in ovarian cancer metastasis via single-cell sequencing and their prognostic implications
Objective This study aims to analyze the differential distribution of immune cells in primary ovari-an cancer and metastatic ovarian cancer,and to explore the differential changes of neutrophils and mast cells in different types of ovarian cancer and their impact on prognosis.Methods Single-cell RNA sequencing(scRNA-seq)data of ovarian cancer cells were downloaded from Gene Expression Omnibus(GEO)database,and the data were used for dimensionality reduction and cluster analysis of primary group and metastasis group to construct Seurat objects and filter data.Subsequently,immune cell types to choose T cells(T cell),natural killer cells(NK cells),Plasma cells,(Plasma)B cells(B cells)and myeloid dendritic cells(mDC),neutrophils and Mast cells(Mast).The uniform manifold approximation and projection(UMAP)algorithm was employed for re-clustering of immune cells,and cell-cell interactions were analyzed using the cell call package.Differential expression analysis of neutrophils and Mast was conducted,followed by correlation with transcriptomic data.Gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)enrichment analyses were performed to explore the roles of these genes in biological processes and pathways.Finally,the Kaplan-Meier survival database was utilized to analyze the correlation between these genes and the prognosis of ovarian cancer patients.Results The immune cell analysis revealed a significant increase in the number of neutrophils and Mast in the metastatic group.Clustering analysis elucidated the distribution of different sub-groups,while the analysis of cell interactions showed a significant increase in interactions between Mast and neutrophils in the metastatic group.Differential expression analysis highlighted key gene expression changes in neutrophils and Mast in ovarian cancer.Among these differentially expressed genes,there are 90 in neutro-phils and 167 in Mast.GO and KEGG analysis mainly focused on mitochondrial metabolism,oxidative phos-phorylation,immune cytokine regulation,lipid metabolism and other related functions and pathways.Kap-lan-Meier analysis indicated that the expression levels of genes such as selectin L(SELL),C-C Motif chemo-kine receptor 7(CCR7),CD2 molecule(CD2),C-C motif chemokine receptor 2(CCR2),C-Cmotif chemo-kine ligand 5(CCL5),and Protein tyrosine phosphatase peceptor type C(PTPRC)were significantly associ-ated with overall survival and recurrence-free survival of patients.Conclusion By analyzing the distribution differences of neutrophils and Mast between primary and metastatic ovarian cancer,this study revealed the role of neutrophils and Mast in promoting ovarian cancer metastasis,thus providing new theoretical basis and potential therapeutic targets for clinical treatment and prognosis judgment of ovarian cancer.
Single-cell RNA sequencingMetastasisNeutrophilsMast cellsOvarian cancer
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