Objective:Immature vasculature lacking pericyte coverage substantially contributes to tumor growth,drug resistance,and cancer cell dissemination.We previously demonstrated that tumor necrosis factor superfamily 15(TNF...Objective:Immature vasculature lacking pericyte coverage substantially contributes to tumor growth,drug resistance,and cancer cell dissemination.We previously demonstrated that tumor necrosis factor superfamily 15(TNFSF15)is a cytokine with important roles in modulating hematopoiesis and vascular homeostasis.The main purpose of this study was to explore whether TNFSF15 might promote freshly isolated myeloid cells to differentiate into CD11b^(+) cells and further into pericytes.Methods:A model of Lewis lung cancer was established in mice with red fluorescent bone marrow.After TNFSF15 treatment,CD11b^(+) myeloid cells and vascular pericytes in the tumors,and the co-localization of pericytes and vascular endothelial cells,were assessed.Additionally,CD11b^(+) cells were isolated from wild-type mice and treated with TNFSF15 to determine the effects on the differentiation of these cells.Results:We observed elevated percentages of bone marrow-derived CD11b^(+)myeloid cells and vascular pericytes in TNFSF15-treated tumors,and the latter cells co-localized with vascular endothelial cells.TNFSF15 protected against CD11b^(+)cell apoptosis and facilitated the differentiation of these cells into pericytes by down-regulating Wnt3a-VEGFR1 and up-regulating CD49e-FN signaling pathways.Conclusions:TNFSF15 facilitates the production of CD11b^(+) cells in the bone marrow and promotes the differentiation of these cells into pericytes,which may stabilize the tumor neovasculature.展开更多
Objective:The aim of this study was to identify hub genes associated with immune cell infiltration in breast cancer through bioinformatic analyses of multiple datasets.Methods:Nonparametric(NOISeq)and robust rank aggr...Objective:The aim of this study was to identify hub genes associated with immune cell infiltration in breast cancer through bioinformatic analyses of multiple datasets.Methods:Nonparametric(NOISeq)and robust rank aggregation-ranked parametric(EdgeR)methods were used to assess robust differentially expressed genes across multiple datasets.Protein-protein interaction network,GO,KEGG enrichment,and subnetwork analyses were performed to identify immune-associated hub genes in breast cancer.Immune cell infiltration was evaluated with the CIBERSORT,XCELL,and TIMER methods.The association between the hub gene-based risk signature and survival was determined through Kaplan–Meier survival analysis,multivariate Cox analysis,and a nomogram with external verification.Results:We identified 163 robust differentially expressed genes in breast cancer through applying both nonparametric and parametric methods to multiple GEO(n=2,212)and TCGA(n=1,045)datasets.Integrated bioinformatic analyses further identified 10 hub genes:CXCL10,CXCL9,CXCL11,SPP1,POSTN,MMP9,DPT,COL1A1,ADAMDEC1,and RGS1.The 10 hub-gene-based risk signature significantly correlated with the prognosis of patients with breast cancer.Moreover,these hub genes were strongly associated with the extent of infiltration of CD4+T cells,CD8+T cells,neutrophils,macrophages,and myeloid dendritic cells into breast tumors.Conclusions:Integrated analyses of multiple databases led to the discovery of 10 robust hub genes that together may serve as a risk factor characteristic of the immune microenvironment in breast cancer.展开更多
基金supported partly by the National Natural Science Foundation of China(Grant Nos.82073064 and 81874167 to LYL,and 82073233 to ZQZ)Haihe Laboratory of Cell Ecosystem Innovation Fund(Grant No.22HHXBSS00020 to LYL)Ministry of Education 111 Project(Grant No.B20016 to LYL)。
文摘Objective:Immature vasculature lacking pericyte coverage substantially contributes to tumor growth,drug resistance,and cancer cell dissemination.We previously demonstrated that tumor necrosis factor superfamily 15(TNFSF15)is a cytokine with important roles in modulating hematopoiesis and vascular homeostasis.The main purpose of this study was to explore whether TNFSF15 might promote freshly isolated myeloid cells to differentiate into CD11b^(+) cells and further into pericytes.Methods:A model of Lewis lung cancer was established in mice with red fluorescent bone marrow.After TNFSF15 treatment,CD11b^(+) myeloid cells and vascular pericytes in the tumors,and the co-localization of pericytes and vascular endothelial cells,were assessed.Additionally,CD11b^(+) cells were isolated from wild-type mice and treated with TNFSF15 to determine the effects on the differentiation of these cells.Results:We observed elevated percentages of bone marrow-derived CD11b^(+)myeloid cells and vascular pericytes in TNFSF15-treated tumors,and the latter cells co-localized with vascular endothelial cells.TNFSF15 protected against CD11b^(+)cell apoptosis and facilitated the differentiation of these cells into pericytes by down-regulating Wnt3a-VEGFR1 and up-regulating CD49e-FN signaling pathways.Conclusions:TNFSF15 facilitates the production of CD11b^(+) cells in the bone marrow and promotes the differentiation of these cells into pericytes,which may stabilize the tumor neovasculature.
基金supported by grants from the National Natural Science Foundation of China(Grant Nos.81874167 and 82073064).
文摘Objective:The aim of this study was to identify hub genes associated with immune cell infiltration in breast cancer through bioinformatic analyses of multiple datasets.Methods:Nonparametric(NOISeq)and robust rank aggregation-ranked parametric(EdgeR)methods were used to assess robust differentially expressed genes across multiple datasets.Protein-protein interaction network,GO,KEGG enrichment,and subnetwork analyses were performed to identify immune-associated hub genes in breast cancer.Immune cell infiltration was evaluated with the CIBERSORT,XCELL,and TIMER methods.The association between the hub gene-based risk signature and survival was determined through Kaplan–Meier survival analysis,multivariate Cox analysis,and a nomogram with external verification.Results:We identified 163 robust differentially expressed genes in breast cancer through applying both nonparametric and parametric methods to multiple GEO(n=2,212)and TCGA(n=1,045)datasets.Integrated bioinformatic analyses further identified 10 hub genes:CXCL10,CXCL9,CXCL11,SPP1,POSTN,MMP9,DPT,COL1A1,ADAMDEC1,and RGS1.The 10 hub-gene-based risk signature significantly correlated with the prognosis of patients with breast cancer.Moreover,these hub genes were strongly associated with the extent of infiltration of CD4+T cells,CD8+T cells,neutrophils,macrophages,and myeloid dendritic cells into breast tumors.Conclusions:Integrated analyses of multiple databases led to the discovery of 10 robust hub genes that together may serve as a risk factor characteristic of the immune microenvironment in breast cancer.
