目的:分析酰基辅酶A结合结构域蛋白3(acyl CoA binding domain containing protein 3,ACBD3)在乳腺癌组织中的表达及其与患者预后的相关性。方法:选择2013年01月至2014年05月我院收治的乳腺癌患者54例,获取相应癌组织样本及癌旁组织样本...目的:分析酰基辅酶A结合结构域蛋白3(acyl CoA binding domain containing protein 3,ACBD3)在乳腺癌组织中的表达及其与患者预后的相关性。方法:选择2013年01月至2014年05月我院收治的乳腺癌患者54例,获取相应癌组织样本及癌旁组织样本各54份。采用免疫组化法检测两组组织标本中ACBD3的表达情况,并分析ACBD3表达与乳腺癌患者病理因素的关系。对不同ACBD3表达情况乳腺癌患者随访5年的生存情况进行讨论。结果:ACBD3在乳腺癌组织中的表达量明显高于癌旁组织[(0.325±0.113)vs(0.058±0.012)](P<0.05);ACBD3的高表达与患者年龄、病理类型、肿瘤直径无关(P>0.05),与组织分化情况、淋巴结转移、TNM分期有关(P<0.05);随访5年,ACBD3高表达患者存活率明显低于ACBD3低表达患者(62.07%vs 88.00%)(P<0.05);ACBD3高表达患者5年无进展生存(PFS)率明显低于ACBD3低表达患者(37.93%vs 68.00%)。结论:乳腺癌组织中ACBD3的表达水平明显增加,ACBD3高表达与乳腺癌发展及转移关系密切,且其对患者预后具有一定判断价值。展开更多
Glycosphingolipid (GSL) metabolism is involved in various physiological processes, including all major cell signaling pathways, and its dysregulation is linked to some diseases. The four-phosphate adaptor protein FAPP...Glycosphingolipid (GSL) metabolism is involved in various physiological processes, including all major cell signaling pathways, and its dysregulation is linked to some diseases. The four-phosphate adaptor protein FAPP2-mediated glucosylceramide (GlcCer) transport for complex GSL synthesis has been studied extensively. However, the molecular machinery of FAPP2 as a GlcCer-transferring protein remains poorly defined. Here, we identify a Golgi-resident protein, acyl-coenzyme A binding domain containing 3 (ACBD3), as an interacting partner of FAPP2. We find that ACBD3 knockdown leads to dramatic Golgi fragmentation, which subsequently causes FAPP2 dispersal throughout the cytoplasm and a decreased localization at trans-Golgi network. The further quantitative Upidomic analysis indicates that ACBD3 knockdown triggers abnormal sphingolipid metabolism. Interestingly, the expression of siRNA-resistant full-length ACBD3 can rescue these defects caused by ACBD3 knockdown. These data reveal critical roles for ACBD3 in maintaining the integrity of Golgi morphology and cellular sphingolipid homeostasis and establish the importance of the integrated Golgi complex for the transfer of GlcCer and complex GSL synthesis.展开更多
文摘目的:分析酰基辅酶A结合结构域蛋白3(acyl CoA binding domain containing protein 3,ACBD3)在乳腺癌组织中的表达及其与患者预后的相关性。方法:选择2013年01月至2014年05月我院收治的乳腺癌患者54例,获取相应癌组织样本及癌旁组织样本各54份。采用免疫组化法检测两组组织标本中ACBD3的表达情况,并分析ACBD3表达与乳腺癌患者病理因素的关系。对不同ACBD3表达情况乳腺癌患者随访5年的生存情况进行讨论。结果:ACBD3在乳腺癌组织中的表达量明显高于癌旁组织[(0.325±0.113)vs(0.058±0.012)](P<0.05);ACBD3的高表达与患者年龄、病理类型、肿瘤直径无关(P>0.05),与组织分化情况、淋巴结转移、TNM分期有关(P<0.05);随访5年,ACBD3高表达患者存活率明显低于ACBD3低表达患者(62.07%vs 88.00%)(P<0.05);ACBD3高表达患者5年无进展生存(PFS)率明显低于ACBD3低表达患者(37.93%vs 68.00%)。结论:乳腺癌组织中ACBD3的表达水平明显增加,ACBD3高表达与乳腺癌发展及转移关系密切,且其对患者预后具有一定判断价值。
文摘目的乳腺癌作为女性最常见的恶性肿瘤已成为女性肿瘤的第二致死原因,寻找特异性的分子标记物有助于研究乳腺癌发生发展,对于目前乳腺癌防治的基础研究有重要意义。本研究旨在探讨乳腺癌组织ACBD3(Acyl-CoA-binding domain-containing protein 3)蛋白表达及其对乳腺癌增殖、转移和预后影响。方法应用蛋白质印迹法检测正常乳腺上皮细胞和乳腺癌细胞系中ACBD3表达。收集1998-03-01-2016-06-30南阳医学高等专科学校第一附属医院手术切除的321例乳腺癌患者石蜡包埋切片组织,采用免疫组化染色技术检测乳腺癌组织中ACBD3蛋白表达水平,患者临床病例分析和随访资料为基础,采用Kaplan-Meier法分析ACBD3高表达与乳腺癌预后的关系;采用免疫组化染色技术检测高表达和低表达ACBD3蛋白的乳腺癌组织中Ki-67和E-cadherin表达水平,分析ACBD3表达与乳腺癌增殖和转移的相关性。结果ACBD3蛋白在乳腺癌细胞系中的表达相对于正常乳腺细胞均为高表达,P<0.001。乳腺癌组织中ACBD3高表达患者5年生存率为66%,低于ACBD3低表达患者的98%,差异有统计学意义,P<0.001。将临床分期、T分期、N分期等与乳腺癌预后相关的指标和ACBD3纳入Cox比例风险模型分析,ACBD3表达水平的相对危险系数为1.191,P=0.008,表明ACBD3强阳性表达的患者预后差。乳腺癌组织ACBD3高表达的173例患者中,Ki-67表达也高的有99例,E-cadherin表达下降的有139例;ACBD3低表达的148例患者中,Ki-67表达也低的有125例,E-cadherin表达升高的有89例。ACBD3表达与Ki-67表达呈正相关,χ~2=58.824,P<0.001;ACBD3表达与E-cadherin表达呈负相关,χ~2=55.305,P<0.001。结论ACBD3在乳腺癌组织中表达升高,与乳腺癌增殖和转移正相关,有助于评估乳腺癌的病情进展与预后。
基金the National Natural Science Foundation of China (31271517 and 31271518)State Key Laboratory of Molecular Developmental Biology+1 种基金ZHYX (2017zhyx29) of Scientific Research Foundation of the Institute for Translational Medicine of Anhui ProvinceBSKY (XJ201123) of Anhui Medical University.
文摘Glycosphingolipid (GSL) metabolism is involved in various physiological processes, including all major cell signaling pathways, and its dysregulation is linked to some diseases. The four-phosphate adaptor protein FAPP2-mediated glucosylceramide (GlcCer) transport for complex GSL synthesis has been studied extensively. However, the molecular machinery of FAPP2 as a GlcCer-transferring protein remains poorly defined. Here, we identify a Golgi-resident protein, acyl-coenzyme A binding domain containing 3 (ACBD3), as an interacting partner of FAPP2. We find that ACBD3 knockdown leads to dramatic Golgi fragmentation, which subsequently causes FAPP2 dispersal throughout the cytoplasm and a decreased localization at trans-Golgi network. The further quantitative Upidomic analysis indicates that ACBD3 knockdown triggers abnormal sphingolipid metabolism. Interestingly, the expression of siRNA-resistant full-length ACBD3 can rescue these defects caused by ACBD3 knockdown. These data reveal critical roles for ACBD3 in maintaining the integrity of Golgi morphology and cellular sphingolipid homeostasis and establish the importance of the integrated Golgi complex for the transfer of GlcCer and complex GSL synthesis.
