目的评估卵巢癌组织中Grb相关结合蛋白2(Grb-associated binding protein 2,GAB2)的表达及其与预后的关系。方法收集南通大学附属肿瘤医院2013年1月—2016年1月手术切除的119例卵巢癌组织及癌旁组织,利用免疫组织化学染色法检测组织中G...目的评估卵巢癌组织中Grb相关结合蛋白2(Grb-associated binding protein 2,GAB2)的表达及其与预后的关系。方法收集南通大学附属肿瘤医院2013年1月—2016年1月手术切除的119例卵巢癌组织及癌旁组织,利用免疫组织化学染色法检测组织中GAB2的表达情况,并分析其表达量与临床特征和总生存期(Overall survival,OS)的关系。利用Cox比例风险模型分析影响卵巢癌患者OS的危险因素。构建基于Cox比例风险模型的Nomogram预后模型预测卵巢癌患者3年和5年生存率。结果与癌旁组织相比,GAB2在癌组织中表达增加(P<0.001)。我们还发现GAB2表达量与FIGO分期(P=0.004)、初诊时CA125水平(P=0.005)和铂耐药性复发(P<0.001)有关。Kaplan-Meier生存曲线表明GAB2的高表达与患者OS的下降有关(P<0.001)。单因素分析结果显示,GAB2表达量、FIGO分期、初诊时CA125水平和铂耐药性复发与卵巢癌患者OS相关(P<0.05)。多因素分析显示,GAB2表达水平是影响卵巢癌患者OS的独立因素。Nomogram预后模型对卵巢癌患者3年和5年生存率的预测能力较好(C指数为0.801)。结论GAB2的表达水平能预测卵巢癌患者的预后,有望成为卵巢癌治疗的潜在靶点。展开更多
Background:Arteriosclerosis obliterans(ASO)is a major cause of adult limb loss worldwide.Autophagy of vascular endothelial cell(VEC)contributes to the ASO progression.However,the molecular mechanism that controls VEC ...Background:Arteriosclerosis obliterans(ASO)is a major cause of adult limb loss worldwide.Autophagy of vascular endothelial cell(VEC)contributes to the ASO progression.However,the molecular mechanism that controls VEC autophagy remains unclear.In this study,we aimed to explore the role of the GRB2 associated binding protein 1(GAB1)in regulating VEC autophagy.Methods:In vivo and in vitro studies were applied to determine the loss of adapt protein GAB1 in association with ASO progression.Histological GAB1 expression was measured in sclerotic vascular intima and normal vascular intima.Gain-and loss-of-function of GAB1 were applied in VEC to determine the effect and potential downstream signaling of GAB1.Results:The autophagy repressor p62 was significantly downregulated in ASO intima as compared to that in healthy donor(0.80 vs.0.20,t=6.43,P<0.05).The expression level of GAB1 mRNA(1.00 vs.0.24,t=7.41,P<0.05)and protein(0.72 vs.0.21,t=5.97,P<0.05)was significantly decreased in ASO group as compared with the control group.Loss of GAB1 led to a remarkable decrease in LC3II(1.19 vs.0.68,t=5.99,P<0.05),whereas overexpression of GAB1 significantly led to a decrease in LC3II level(0.41 vs.0.93,t=7.12,P<0.05).Phosphorylation levels of JNK and p38 were significantly associated with gain-and loss-of-function of GAB1 protein.Conclusion:Loss of GAB1 promotes VEC autophagy which is associated with ASO.GAB1 and its downstream signaling might be potential therapeutic targets for ASO treatment.展开更多
文摘目的评估卵巢癌组织中Grb相关结合蛋白2(Grb-associated binding protein 2,GAB2)的表达及其与预后的关系。方法收集南通大学附属肿瘤医院2013年1月—2016年1月手术切除的119例卵巢癌组织及癌旁组织,利用免疫组织化学染色法检测组织中GAB2的表达情况,并分析其表达量与临床特征和总生存期(Overall survival,OS)的关系。利用Cox比例风险模型分析影响卵巢癌患者OS的危险因素。构建基于Cox比例风险模型的Nomogram预后模型预测卵巢癌患者3年和5年生存率。结果与癌旁组织相比,GAB2在癌组织中表达增加(P<0.001)。我们还发现GAB2表达量与FIGO分期(P=0.004)、初诊时CA125水平(P=0.005)和铂耐药性复发(P<0.001)有关。Kaplan-Meier生存曲线表明GAB2的高表达与患者OS的下降有关(P<0.001)。单因素分析结果显示,GAB2表达量、FIGO分期、初诊时CA125水平和铂耐药性复发与卵巢癌患者OS相关(P<0.05)。多因素分析显示,GAB2表达水平是影响卵巢癌患者OS的独立因素。Nomogram预后模型对卵巢癌患者3年和5年生存率的预测能力较好(C指数为0.801)。结论GAB2的表达水平能预测卵巢癌患者的预后,有望成为卵巢癌治疗的潜在靶点。
基金supported by the grants from the Shanghai Municipal Science and Technology Commission(No.14430721400)National Natural Science Foundation(Nos.81700421 and 81670442)Clinical innovative research funding of Shanghai Jiaotong University School of Medicine(No.PY2018-IIC-05)。
文摘Background:Arteriosclerosis obliterans(ASO)is a major cause of adult limb loss worldwide.Autophagy of vascular endothelial cell(VEC)contributes to the ASO progression.However,the molecular mechanism that controls VEC autophagy remains unclear.In this study,we aimed to explore the role of the GRB2 associated binding protein 1(GAB1)in regulating VEC autophagy.Methods:In vivo and in vitro studies were applied to determine the loss of adapt protein GAB1 in association with ASO progression.Histological GAB1 expression was measured in sclerotic vascular intima and normal vascular intima.Gain-and loss-of-function of GAB1 were applied in VEC to determine the effect and potential downstream signaling of GAB1.Results:The autophagy repressor p62 was significantly downregulated in ASO intima as compared to that in healthy donor(0.80 vs.0.20,t=6.43,P<0.05).The expression level of GAB1 mRNA(1.00 vs.0.24,t=7.41,P<0.05)and protein(0.72 vs.0.21,t=5.97,P<0.05)was significantly decreased in ASO group as compared with the control group.Loss of GAB1 led to a remarkable decrease in LC3II(1.19 vs.0.68,t=5.99,P<0.05),whereas overexpression of GAB1 significantly led to a decrease in LC3II level(0.41 vs.0.93,t=7.12,P<0.05).Phosphorylation levels of JNK and p38 were significantly associated with gain-and loss-of-function of GAB1 protein.Conclusion:Loss of GAB1 promotes VEC autophagy which is associated with ASO.GAB1 and its downstream signaling might be potential therapeutic targets for ASO treatment.
