Background:S100A8 is a member of the S100 protein family and plays a pivotal role in regulating inflammation and tumor progression.This study aimed to comprehensively assess the expression patterns and functional role...Background:S100A8 is a member of the S100 protein family and plays a pivotal role in regulating inflammation and tumor progression.This study aimed to comprehensively assess the expression patterns and functional roles of S100A8 in glioma progression.Methods:Glioma tissues were collected from 98 patients who underwent surgical treatment at Fudan University Shanghai Cancer Center.S100A8 expression in glioma tissues was analyzed using immunohistochemistry(IHC)to establish its correlation with clinicopathological features in patients.The expression and prognostic effect of S100A8 in glioma were analyzed using TCGA and CGGA public databases.Then,we investigated the role of S100A8 in glioma through a series of in vivo and in vitro experiments including Transwell,wound healing,CCK8,and intracranial tumor models.Subsequently,bioinformatics analysis,single-cell sequencing and coimmunopre-cipitation(Co-IP)were used to explore the underlying mechanism.Results:S100A8 was upregulated in gliomas compared to paracancerous tissues,and this phenotype was sig-nificantly correlated with poor prognosis.Subgroup analysis showed that S100A8 expression was higher in the high-grade glioma(HGG)group than that in the low-grade glioma(LGG)group.S100A8 overexpression in glioma cell lines promoted cell proliferation,migration and invasion,while silencing S100A8 reversed these effects.In vivo experiments showed that S100A8 knockdown can significantly reduce the tumor burden of glioma cells.Notably,S100A8 was observed to stimulate microglial M2 polarization by interacting with TLR4,which subse-quently induced NF-𝜅B signaling and IL-10 secretion within the tumor microenvironment.Conclusions:S100A8 promotes tumor progression by inducing phenotypic polarization of microglia through the TLR4/IL-10 signaling pathway in glioma.It might represent a therapeutic target for further basic research or clinical management of glioma.展开更多
目的探究血清S100钙结合蛋白A8(S100A8)和程序性死亡配体-1(PD-L1)联合超声检测在子宫内膜癌诊断及预后中的价值。方法选取2020年4月至2022年4月于我院收治的确诊为子宫内膜癌的患者166例即为癌症组,按照国际妇产科联合会(FIGO)标准分...目的探究血清S100钙结合蛋白A8(S100A8)和程序性死亡配体-1(PD-L1)联合超声检测在子宫内膜癌诊断及预后中的价值。方法选取2020年4月至2022年4月于我院收治的确诊为子宫内膜癌的患者166例即为癌症组,按照国际妇产科联合会(FIGO)标准分为Ⅰ期48例、Ⅱ期52例、Ⅲ期42例、Ⅳ期24例。选择同期在我院确诊为子宫内膜增生的患者166例为对照组;使用酶联免疫吸附试验(ELISA)检测血清中S100A8和PD-L1水平;使用阴道超声获取血流频谱测得血流参数:搏动指数(PI)、阻力指数(RI)。采用受试者工作特征(ROC)曲线分析血清S100A8和PD-L1联合超声参数对子宫内膜癌的诊断价值以及预后的预测价值。结果与对照组相比,癌症组患者血清中S100A8和PD-L1水平显著升高(t=10.688、8.605,均P<0.001);与Ⅰ期相比,Ⅱ期、Ⅲ期、Ⅳ期患者血清中S100A8和PD-L1水平显著升高,与Ⅱ期相比,Ⅳ期患者血清中S100A8和PD-L1水平显著升高(P<0.05)。与对照组相比,癌症组PI和RI的值显著降低(t=7.183、6.799,均P<0.001);血清S100A8和PD-L1联合超声参数对子宫内膜癌诊断的曲线下面积(AUC)高于各指标单独诊断的AUC值(Z S100A8 vs.S100A8+PD-L1+PI+RI=6.472,Z PD-L1 vs.S100A8+PD-L1+PI+RI=6.903,Z PI vs.S100A8+PD-L1+PI+RI=7.072,Z RI vs.S100A8+PD-L1+PI+RI=5.987,均P<0.001);与预后良好组相比,预后不良组S100A8、PD-L1水平显著升高,PI、RI水平显著降低(P<0.001);血清S100A8和PD-L1联合超声参数对子宫内膜癌预后预测的AUC高于各指标单独预测的AUC值(Z S100A8 vs.S100A8+PD-L1+PI+RI=2.841,P=0.005;Z PD-L1 vs.S100A8+PD-L1+PI+RI=2.146,P=0.032;Z PI vs.S100A8+PD-L1+PI+RI=6.056,P<0.001;Z RI vs.S100A8+PD-L1+PI+RI=4.370,P<0.001)。结论子宫内膜癌患者血清中S100A8和PD-L1水平显著升高,血清S100A8和PD-L1联合超声能够提高对子宫内膜癌诊断及预后价值。展开更多
基金supported by the National Natural Science Foundation of China(grant numbers:82103429 and 82173177).
文摘Background:S100A8 is a member of the S100 protein family and plays a pivotal role in regulating inflammation and tumor progression.This study aimed to comprehensively assess the expression patterns and functional roles of S100A8 in glioma progression.Methods:Glioma tissues were collected from 98 patients who underwent surgical treatment at Fudan University Shanghai Cancer Center.S100A8 expression in glioma tissues was analyzed using immunohistochemistry(IHC)to establish its correlation with clinicopathological features in patients.The expression and prognostic effect of S100A8 in glioma were analyzed using TCGA and CGGA public databases.Then,we investigated the role of S100A8 in glioma through a series of in vivo and in vitro experiments including Transwell,wound healing,CCK8,and intracranial tumor models.Subsequently,bioinformatics analysis,single-cell sequencing and coimmunopre-cipitation(Co-IP)were used to explore the underlying mechanism.Results:S100A8 was upregulated in gliomas compared to paracancerous tissues,and this phenotype was sig-nificantly correlated with poor prognosis.Subgroup analysis showed that S100A8 expression was higher in the high-grade glioma(HGG)group than that in the low-grade glioma(LGG)group.S100A8 overexpression in glioma cell lines promoted cell proliferation,migration and invasion,while silencing S100A8 reversed these effects.In vivo experiments showed that S100A8 knockdown can significantly reduce the tumor burden of glioma cells.Notably,S100A8 was observed to stimulate microglial M2 polarization by interacting with TLR4,which subse-quently induced NF-𝜅B signaling and IL-10 secretion within the tumor microenvironment.Conclusions:S100A8 promotes tumor progression by inducing phenotypic polarization of microglia through the TLR4/IL-10 signaling pathway in glioma.It might represent a therapeutic target for further basic research or clinical management of glioma.
文摘目的探究血清S100钙结合蛋白A8(S100A8)和程序性死亡配体-1(PD-L1)联合超声检测在子宫内膜癌诊断及预后中的价值。方法选取2020年4月至2022年4月于我院收治的确诊为子宫内膜癌的患者166例即为癌症组,按照国际妇产科联合会(FIGO)标准分为Ⅰ期48例、Ⅱ期52例、Ⅲ期42例、Ⅳ期24例。选择同期在我院确诊为子宫内膜增生的患者166例为对照组;使用酶联免疫吸附试验(ELISA)检测血清中S100A8和PD-L1水平;使用阴道超声获取血流频谱测得血流参数:搏动指数(PI)、阻力指数(RI)。采用受试者工作特征(ROC)曲线分析血清S100A8和PD-L1联合超声参数对子宫内膜癌的诊断价值以及预后的预测价值。结果与对照组相比,癌症组患者血清中S100A8和PD-L1水平显著升高(t=10.688、8.605,均P<0.001);与Ⅰ期相比,Ⅱ期、Ⅲ期、Ⅳ期患者血清中S100A8和PD-L1水平显著升高,与Ⅱ期相比,Ⅳ期患者血清中S100A8和PD-L1水平显著升高(P<0.05)。与对照组相比,癌症组PI和RI的值显著降低(t=7.183、6.799,均P<0.001);血清S100A8和PD-L1联合超声参数对子宫内膜癌诊断的曲线下面积(AUC)高于各指标单独诊断的AUC值(Z S100A8 vs.S100A8+PD-L1+PI+RI=6.472,Z PD-L1 vs.S100A8+PD-L1+PI+RI=6.903,Z PI vs.S100A8+PD-L1+PI+RI=7.072,Z RI vs.S100A8+PD-L1+PI+RI=5.987,均P<0.001);与预后良好组相比,预后不良组S100A8、PD-L1水平显著升高,PI、RI水平显著降低(P<0.001);血清S100A8和PD-L1联合超声参数对子宫内膜癌预后预测的AUC高于各指标单独预测的AUC值(Z S100A8 vs.S100A8+PD-L1+PI+RI=2.841,P=0.005;Z PD-L1 vs.S100A8+PD-L1+PI+RI=2.146,P=0.032;Z PI vs.S100A8+PD-L1+PI+RI=6.056,P<0.001;Z RI vs.S100A8+PD-L1+PI+RI=4.370,P<0.001)。结论子宫内膜癌患者血清中S100A8和PD-L1水平显著升高,血清S100A8和PD-L1联合超声能够提高对子宫内膜癌诊断及预后价值。
