Objective:Hepatocellular carcinoma(HCC),the main type of liver cancer,has a high morbidity and mortality,and a poor prognosis.RNA helicase DDX5,which acts as a transcriptional co-regulator,is overexpressed in most mal...Objective:Hepatocellular carcinoma(HCC),the main type of liver cancer,has a high morbidity and mortality,and a poor prognosis.RNA helicase DDX5,which acts as a transcriptional co-regulator,is overexpressed in most malignant tumors and promotes cancer cell growth.Heat shock protein 90(HSP90)is an important molecular chaperone in the conformational maturation and stabilization of numerous proteins involved in cell growth or survival.Methods:DDX5 m RNA and protein expression in surgically resected HCC tissues from 24 Asian patients were detected by quantitative real-time PCR and Western blot,respectively.The interaction of DDX5-HSP90 was determined by molecular docking,immunoprecipitation,and laser scanning confocal microscopy.The autophagy signal was detected by Western blot.The cell functions and signaling pathways of DDX5 were determined in 2 HCC cell lines.Two different murine HCC xenograft models were used to determine the function of DDX5 and the therapeutic effect of an HSP90 inhibitor.Results:HSP90 interacted directly with DDX5 and inhibited DDX5 protein degradation in the AMPK/ULK1-regulated autophagy pathway.The subsequent accumulation of DDX5 protein induced the malignant phenotype of HCC by activating theβ-catenin signaling pathway.The silencing of DDX5 or treatment with HSP90 inhibitor both blocked in vivo tumor growth in a murine HCC xenograft model.High levels of HSP90 and DDX5 protein were associated with poor prognoses.Conclusions:HSP90 interacted with DDX5 protein and subsequently protected DDX5 protein from AMPK/ULK1-regulated autophagic degradation.DDX5 and HSP90 are therefore potential therapeutic targets for HCC.展开更多
目的研究磁共振成像(MRI)联合血清着丝粒结合蛋白U(CENPU)、热休克蛋白90α(HSP90α)在乳腺癌诊断中的临床价值。方法选取2021年1月至2023年4月在本院就诊的疑似乳腺癌患者227例进行研究,以术后病理诊断结果作为金标准,将227例疑似乳腺...目的研究磁共振成像(MRI)联合血清着丝粒结合蛋白U(CENPU)、热休克蛋白90α(HSP90α)在乳腺癌诊断中的临床价值。方法选取2021年1月至2023年4月在本院就诊的疑似乳腺癌患者227例进行研究,以术后病理诊断结果作为金标准,将227例疑似乳腺癌患者分为乳腺癌组143例,良性肿瘤组84例。对所有患者进行MRI检查,酶联免疫法检测血清HSP90α水平,qRT-PCR法检测血清CENPU水平。ROC曲线分析血清CENPU、HSP90α水平对乳腺癌的诊断价值,四表格法分析MRI检测及其联合血清CENPU、HSP90α水平对乳腺癌的诊断价值。结果乳腺癌组血清CENPU、HSP90α水平显著高于良性肿瘤组,差异具有统计学意义(P<0.05)。血清CENPU水平诊断乳腺癌的AUC为0.739,敏感性为65.73%,特异性为76.19%;HSP90α水平诊断乳腺癌的AUC为0.767,敏感性为79.72%,特异性为64.29%。MRI检查结果显示,乳腺癌患者137例,良性肿瘤患者90例;检出浸润性导管癌50例,乳腺导管内原位癌47例,乳头状瘤27例,浸润性小叶癌13例。MRI检查乳腺癌的敏感性为76.92%,特异性为67.86%,准确度为73.57%;MRI检查对乳腺癌的诊断结果与病理诊断结果具有一致性(Kappa值=0.441,P<0.05)。M R I联合血清C E N P U、HSP90α水平诊断乳腺癌的敏感性为98.60%,特异性为63.10%,准确度为85.46%;三者联合对乳腺癌的诊断结果与病理诊断结果具有较好一致性(Kappa=0.664,P<0.05);MRI联合血清CENPU、HSP90α水平诊断乳腺癌的敏感性和准确度显著高于MRI、CENPU、HSP90α单独诊断(P<0.05)。结论MRI联合血清CENPU、HSP90α对乳腺癌诊断具有重要临床价值。展开更多
目的探讨多模态磁共振成像(M R I)联合血清人生长分化因子3(GDF3)、热休克蛋白-90α(HSP90A)诊断乳腺癌(BRCA)的临床价值。方法收集2017年1月-2020年12月间在本院健康检查后怀疑为BRCA的96例乳腺疾病患者作为研究对象。以术后病理或穿...目的探讨多模态磁共振成像(M R I)联合血清人生长分化因子3(GDF3)、热休克蛋白-90α(HSP90A)诊断乳腺癌(BRCA)的临床价值。方法收集2017年1月-2020年12月间在本院健康检查后怀疑为BRCA的96例乳腺疾病患者作为研究对象。以术后病理或穿刺活检结果为标准,将疑似患者分为BRCA组65例,良性组31例。所有受试者接受多模态MRI检查;酶联免疫吸附法检测血清GDF3、HSP90A水平,ROC和四表格分析多模态MRI、血清GDF3、HSP90A水平单独及联合诊断BRCA的价值。结果BRCA组Ktrans、Kep、MD显著高于良性组,ADCslow、ADCfast、MK均低于良性组(P<0.05);DCE-MRI、IVIM及DKI参数(Kep、ADCslow及MK值)诊断BRCA的AUC分别为0.724、0.730、0.652,DCEMRI+IVIM+DKI的诊断效能高于单一模型(Z=2.287~3.793,P=0.001~0.022),AUC为0.839。BRCA组血清GDF3、HSP90A水平均显著高于良性组(P<0.05);血清GDF3、HSP90A水平诊断BRCA的AUC为0.828、0.817,敏感度、70.77%、66.15%;特异度分别为83.87%、93.55%。多模态MRI联合血清GDF3、HSP90A检出假阳性6例,假阴性6例,Kappa值为0.714(P<0.05),与病理结果一致性较高,联合诊断BRCA的灵敏度、阴性预测值及准确度明显高于多模态MRI、血清GDF3、HSP90A单独诊断(P<0.05)。结论多模态MRI联合血清GDF3、HSP90A水平诊断BRCA具有较高的敏感度和准确度,具有一定临床应用价值。展开更多
基金funding support from the National Natural Science Foundation of China(Grant Nos.81672467,81702773,81702389,and 81672368)the Major National R&D Project(Grant Nos.2018ZX10723204,2018ZX10302205,and 2018ZX09J18107)the Natural Science Foundation of Beijing(Grant No.7172207)。
文摘Objective:Hepatocellular carcinoma(HCC),the main type of liver cancer,has a high morbidity and mortality,and a poor prognosis.RNA helicase DDX5,which acts as a transcriptional co-regulator,is overexpressed in most malignant tumors and promotes cancer cell growth.Heat shock protein 90(HSP90)is an important molecular chaperone in the conformational maturation and stabilization of numerous proteins involved in cell growth or survival.Methods:DDX5 m RNA and protein expression in surgically resected HCC tissues from 24 Asian patients were detected by quantitative real-time PCR and Western blot,respectively.The interaction of DDX5-HSP90 was determined by molecular docking,immunoprecipitation,and laser scanning confocal microscopy.The autophagy signal was detected by Western blot.The cell functions and signaling pathways of DDX5 were determined in 2 HCC cell lines.Two different murine HCC xenograft models were used to determine the function of DDX5 and the therapeutic effect of an HSP90 inhibitor.Results:HSP90 interacted directly with DDX5 and inhibited DDX5 protein degradation in the AMPK/ULK1-regulated autophagy pathway.The subsequent accumulation of DDX5 protein induced the malignant phenotype of HCC by activating theβ-catenin signaling pathway.The silencing of DDX5 or treatment with HSP90 inhibitor both blocked in vivo tumor growth in a murine HCC xenograft model.High levels of HSP90 and DDX5 protein were associated with poor prognoses.Conclusions:HSP90 interacted with DDX5 protein and subsequently protected DDX5 protein from AMPK/ULK1-regulated autophagic degradation.DDX5 and HSP90 are therefore potential therapeutic targets for HCC.
文摘目的研究磁共振成像(MRI)联合血清着丝粒结合蛋白U(CENPU)、热休克蛋白90α(HSP90α)在乳腺癌诊断中的临床价值。方法选取2021年1月至2023年4月在本院就诊的疑似乳腺癌患者227例进行研究,以术后病理诊断结果作为金标准,将227例疑似乳腺癌患者分为乳腺癌组143例,良性肿瘤组84例。对所有患者进行MRI检查,酶联免疫法检测血清HSP90α水平,qRT-PCR法检测血清CENPU水平。ROC曲线分析血清CENPU、HSP90α水平对乳腺癌的诊断价值,四表格法分析MRI检测及其联合血清CENPU、HSP90α水平对乳腺癌的诊断价值。结果乳腺癌组血清CENPU、HSP90α水平显著高于良性肿瘤组,差异具有统计学意义(P<0.05)。血清CENPU水平诊断乳腺癌的AUC为0.739,敏感性为65.73%,特异性为76.19%;HSP90α水平诊断乳腺癌的AUC为0.767,敏感性为79.72%,特异性为64.29%。MRI检查结果显示,乳腺癌患者137例,良性肿瘤患者90例;检出浸润性导管癌50例,乳腺导管内原位癌47例,乳头状瘤27例,浸润性小叶癌13例。MRI检查乳腺癌的敏感性为76.92%,特异性为67.86%,准确度为73.57%;MRI检查对乳腺癌的诊断结果与病理诊断结果具有一致性(Kappa值=0.441,P<0.05)。M R I联合血清C E N P U、HSP90α水平诊断乳腺癌的敏感性为98.60%,特异性为63.10%,准确度为85.46%;三者联合对乳腺癌的诊断结果与病理诊断结果具有较好一致性(Kappa=0.664,P<0.05);MRI联合血清CENPU、HSP90α水平诊断乳腺癌的敏感性和准确度显著高于MRI、CENPU、HSP90α单独诊断(P<0.05)。结论MRI联合血清CENPU、HSP90α对乳腺癌诊断具有重要临床价值。
文摘目的探讨多模态磁共振成像(M R I)联合血清人生长分化因子3(GDF3)、热休克蛋白-90α(HSP90A)诊断乳腺癌(BRCA)的临床价值。方法收集2017年1月-2020年12月间在本院健康检查后怀疑为BRCA的96例乳腺疾病患者作为研究对象。以术后病理或穿刺活检结果为标准,将疑似患者分为BRCA组65例,良性组31例。所有受试者接受多模态MRI检查;酶联免疫吸附法检测血清GDF3、HSP90A水平,ROC和四表格分析多模态MRI、血清GDF3、HSP90A水平单独及联合诊断BRCA的价值。结果BRCA组Ktrans、Kep、MD显著高于良性组,ADCslow、ADCfast、MK均低于良性组(P<0.05);DCE-MRI、IVIM及DKI参数(Kep、ADCslow及MK值)诊断BRCA的AUC分别为0.724、0.730、0.652,DCEMRI+IVIM+DKI的诊断效能高于单一模型(Z=2.287~3.793,P=0.001~0.022),AUC为0.839。BRCA组血清GDF3、HSP90A水平均显著高于良性组(P<0.05);血清GDF3、HSP90A水平诊断BRCA的AUC为0.828、0.817,敏感度、70.77%、66.15%;特异度分别为83.87%、93.55%。多模态MRI联合血清GDF3、HSP90A检出假阳性6例,假阴性6例,Kappa值为0.714(P<0.05),与病理结果一致性较高,联合诊断BRCA的灵敏度、阴性预测值及准确度明显高于多模态MRI、血清GDF3、HSP90A单独诊断(P<0.05)。结论多模态MRI联合血清GDF3、HSP90A水平诊断BRCA具有较高的敏感度和准确度,具有一定临床应用价值。
