BACKGROUND The tumor microenvironment(TME)plays an important role in the growth and expansion of gastric cancer(GC).Studies have identified that CD93 is involved in abnormal tumor angiogenesis,which may be related to ...BACKGROUND The tumor microenvironment(TME)plays an important role in the growth and expansion of gastric cancer(GC).Studies have identified that CD93 is involved in abnormal tumor angiogenesis,which may be related to the regulation of the TME.AIM To determine the role of CD93 in GC.METHODS Transcriptomic data of GC was investigated in a cohort from The Cancer Genome Atlas.Additionally,RNA-seq data sets from Gene Expression Omnibus(GSE118916,GSE52138,GSE79973,GSE19826,and GSE84433)were applied to validate the results.We performed the immune infiltration analyses using ESTIMATE,CIBERSORT,and ssGSEA.Furthermore,weighted gene co-expression network analysis(WGCNA)was conducted to identify the immunerelated genes.RESULTS Compared to normal tissues,CD93 significantly enriched in tumor tissues(t=4.669,95%CI:0.342-0.863,P<0.001).Higher expression of CD93 was significantly associated with shorter overall survival(hazard ratio=1.62,95%CI:1.09-2.4,P=0.017),less proportion of CD8 T and activated natural killer cells in the TME(P<0.05),and lower tumor mutation burden(t=4.131,95%CI:0.721-0.256,P<0.001).Genes co-expressed with CD93 were mainly enriched in angiogenesis.Moreover,11 genes were identified with a strong relationship between CD93 and the immune microenvironment using WGCNA.CONCLUSION CD93 is a novel prognostic and diagnostic biomarker for GC,that is closely related to the immune infiltration in the TME.Although this retrospective study was a comprehensive analysis,the prospective cohort studies are preferred to further confirm these conclusions.展开更多
目的:应用生物信息学方法探讨CD93基因在肺鳞癌组织中的表达情况,并分析CD93基因表达与化疗敏感性及患者预后的关系。方法:通过The Cancer Genome Atlas(TCGA)数据库比较CD93 mRNA在肺鳞癌患者与正常肺组织中的表达差异。采用基因集富...目的:应用生物信息学方法探讨CD93基因在肺鳞癌组织中的表达情况,并分析CD93基因表达与化疗敏感性及患者预后的关系。方法:通过The Cancer Genome Atlas(TCGA)数据库比较CD93 mRNA在肺鳞癌患者与正常肺组织中的表达差异。采用基因集富集分析(GSEA)CD93免疫相关通路;采用单样本基因集富集分析(ssGSEA)肺鳞癌患者的CD93基因表达情况与肿瘤微环境免疫细胞浸润的关系;采用pRRophetic算法,以IC50值为指标预测CD93基因表达与化疗药物敏感性的关系,并考察其与肺鳞癌患者预后的关系。结果:与正常肺组织相比,CD93 mRNA在肺鳞癌组织中低表达;CD93高表达的肺鳞癌组织样本显著富集在干扰素α反应、干扰素γ反应等相关信号通路;在肺鳞癌组织中,CD93表达水平与浆细胞样树突状细胞、自然杀伤细胞、巨噬细胞、调节性T细胞、骨髓来源的抑制性细胞浸润水平呈正相关。同时,化疗敏感性表示在肺鳞癌组织中,对于紫杉醇、长春瑞滨、多西他赛、顺铂等化疗药物,高表达CD93组IC50值高于低表达组。KaplanMeier结果显示,CD93表达水平与患者预后密切相关(P<0.05)。结论:CD93在肺鳞癌组织中低表达,对传统化疗药物敏感;且CD93参与免疫相关通路,可作为肺鳞癌新型分子标志物。展开更多
CD93 and GAIP-interacting protein, C termius （GIPC） have been shown to interactively alter phagocytic processes of immune cells. CD93 and GIPC expression and localization during cen-tral nervous system inflammation ...CD93 and GAIP-interacting protein, C termius （GIPC） have been shown to interactively alter phagocytic processes of immune cells. CD93 and GIPC expression and localization during cen-tral nervous system inflammation have not yet been reported. In this study, we established a rat model of brain inlfammation by lipopolysaccharide injection to the lateral ventricle. In the brain of rats with inlfammation, western blots showed increased CD93 expression that decreased over time. GIPC expression was unaltered. Immunohistochemistry demonstrated extensive distribution of CD93 expression mainly in cell membranes in the cerebral cortex. After lipopoly-saccharide stimulation, CD93 expression increased and then reduced, with distinct staining in the cytoplasm and nucleus. Double immunolfuorescence staining in cerebral cortex of normal rats showed that CD93 and GIPC widely expressed in resting microglia and neurons. CD93 was mainly expressed in microglial and neuronal cell membranes, while GIPC was expressed in both cell membrane and cytoplasm. In the cerebral cortex at 9 hours after model establishment, CD93-immunoreactive signal diminished in microglial membrane, with cytoplasmic transloca-tion and aggregation detected. GIPC localization was unaltered in neurons and microglia. These results are the ifrst to demonstrate CD93 participation in pathophysiological processes of central nervous system inlfammation.展开更多
文摘BACKGROUND The tumor microenvironment(TME)plays an important role in the growth and expansion of gastric cancer(GC).Studies have identified that CD93 is involved in abnormal tumor angiogenesis,which may be related to the regulation of the TME.AIM To determine the role of CD93 in GC.METHODS Transcriptomic data of GC was investigated in a cohort from The Cancer Genome Atlas.Additionally,RNA-seq data sets from Gene Expression Omnibus(GSE118916,GSE52138,GSE79973,GSE19826,and GSE84433)were applied to validate the results.We performed the immune infiltration analyses using ESTIMATE,CIBERSORT,and ssGSEA.Furthermore,weighted gene co-expression network analysis(WGCNA)was conducted to identify the immunerelated genes.RESULTS Compared to normal tissues,CD93 significantly enriched in tumor tissues(t=4.669,95%CI:0.342-0.863,P<0.001).Higher expression of CD93 was significantly associated with shorter overall survival(hazard ratio=1.62,95%CI:1.09-2.4,P=0.017),less proportion of CD8 T and activated natural killer cells in the TME(P<0.05),and lower tumor mutation burden(t=4.131,95%CI:0.721-0.256,P<0.001).Genes co-expressed with CD93 were mainly enriched in angiogenesis.Moreover,11 genes were identified with a strong relationship between CD93 and the immune microenvironment using WGCNA.CONCLUSION CD93 is a novel prognostic and diagnostic biomarker for GC,that is closely related to the immune infiltration in the TME.Although this retrospective study was a comprehensive analysis,the prospective cohort studies are preferred to further confirm these conclusions.
基金supported by the National Natural Science Foundation of China,No.31170766the Nantong Municipal Social Undertakings Technological Innovation and Demonstration Project Foundation,No.HS2012032the Natural Science Pre-research Project Foundation of Nantong University in 2012,No.12ZY020
文摘CD93 and GAIP-interacting protein, C termius （GIPC） have been shown to interactively alter phagocytic processes of immune cells. CD93 and GIPC expression and localization during cen-tral nervous system inflammation have not yet been reported. In this study, we established a rat model of brain inlfammation by lipopolysaccharide injection to the lateral ventricle. In the brain of rats with inlfammation, western blots showed increased CD93 expression that decreased over time. GIPC expression was unaltered. Immunohistochemistry demonstrated extensive distribution of CD93 expression mainly in cell membranes in the cerebral cortex. After lipopoly-saccharide stimulation, CD93 expression increased and then reduced, with distinct staining in the cytoplasm and nucleus. Double immunolfuorescence staining in cerebral cortex of normal rats showed that CD93 and GIPC widely expressed in resting microglia and neurons. CD93 was mainly expressed in microglial and neuronal cell membranes, while GIPC was expressed in both cell membrane and cytoplasm. In the cerebral cortex at 9 hours after model establishment, CD93-immunoreactive signal diminished in microglial membrane, with cytoplasmic transloca-tion and aggregation detected. GIPC localization was unaltered in neurons and microglia. These results are the ifrst to demonstrate CD93 participation in pathophysiological processes of central nervous system inlfammation.
