目的观察亮氨酸拉链EFhand结构域跨膜蛋白1(LETM1)在胃癌中的表达情况,判断其对胃癌患者预后的价值。方法应用免疫组化法检测114例胃癌及癌旁正常组织中LETM1的表达,通过电话随访获取患者的预后信息,分析LETM1与胃癌患者临床病理特征及...目的观察亮氨酸拉链EFhand结构域跨膜蛋白1(LETM1)在胃癌中的表达情况,判断其对胃癌患者预后的价值。方法应用免疫组化法检测114例胃癌及癌旁正常组织中LETM1的表达,通过电话随访获取患者的预后信息,分析LETM1与胃癌患者临床病理特征及总体生存率之间的关系。结果胃癌及癌旁正常组织中LETM1的阳性表达率分别为59.65%和15.78%( P< 0.05),且与肿瘤的分化程度( P =0.030)、临床TNM分期( P =0.003)及淋巴结转移( P =0.033)密切相关。预后结果分析显示, LETM1高表达的胃癌患者的3年总体生存率明显低于阴性表达者(χ^2=6.097, P< 0.05)。LETM1的表达水平、临床TNM分期、病理分化程度以及是否淋巴结转移均是胃癌患者预后的独立影响因素,LETM1表达水平高、临床分期晚、分化程度差、淋巴结转移阳性均可导致患者预后不良。结论 LETM1的异常表达与胃癌的发生发展密切相关,可将其作为判断临床预后的新型生物标志物。展开更多
Osteosarcoma is a differentiation-deficient disease,and despite the unique advan-tages and great potential of differentiation therapy,there are only a few known differentia-tion inducers,and little research has been d...Osteosarcoma is a differentiation-deficient disease,and despite the unique advan-tages and great potential of differentiation therapy,there are only a few known differentia-tion inducers,and little research has been done on their targets.Cell differentiation is associated with an increase in mitochondrial content and activity.The metabolism of some tu-mor cells is characterized by impaired oxidative phosphorylation,as well as up-regulation of aerobic glycolysis and pentose phosphate pathways.Leucine-containing zipper and EF-hand transmembrane protein 1(LETM1)is involved in the maintenance of mitochondrial morphology and is closely associated with tumorigenesis and progression,as well as cancer cell stemness.We found that MG63 and 143B osteosarcoma cells overexpress LETM1 and exhibit abnormalities in mitochondrial structure and function.Knockdown of LETM1 partially restored the mitochon-drial structure and function,inhibited the pentose phosphate pathway,promoted oxidative phosphorylation,and led to osteogenic differentiation.It also inhibited spheroid cell forma-tion,proliferation,migration,and invasion in an in vitro model.When LETM1 was knocked down in vivo,there was reduced tumor formation and lung metastasis.These data suggest that mitochondria are aberrant in LETM1-overexpressing osteosarcoma cells,and knockdown of LETM1 partially restores the mitochondrial structure and function,inhibits the pentose phosphate pathway,promotes oxidative phosphorylation,and increases osteogenic differentiation,thereby reducing malignant biological behavior of the cells.展开更多
文摘癌胚抗原(carcinoembryonic antigen,CEA)是一种异常表达于消化系统恶性肿瘤中的酸性糖蛋白,对于消化道恶性肿瘤的诊断和疗效预测具有重要价值。文献报道CEA对于肺癌的诊断灵敏度也较高,且与肿瘤的进展密切相关,能够作为肺癌复发及远处转移的监测指标[1]。亮氨酸拉链EF-hand结构域跨膜蛋白1(LETM1)是一种保守性较强的线粒体内膜蛋白,通过调节线粒体的基本代谢间接调节恶性肿瘤的发生发展,已有多项研究表明LETM1与肿瘤的发生密切相关[2-3]。但目前关于CEAm RNA和LETMl在肺癌患者中的表达情况及其对肺癌患者的预后价值的相关研究较少,因此,本文拟探究CEA m RNA和LETMl在肺癌患者中的表达情况,为临床肺癌预后评估寻找新的分子标志物。
文摘目的观察亮氨酸拉链EFhand结构域跨膜蛋白1(LETM1)在胃癌中的表达情况,判断其对胃癌患者预后的价值。方法应用免疫组化法检测114例胃癌及癌旁正常组织中LETM1的表达,通过电话随访获取患者的预后信息,分析LETM1与胃癌患者临床病理特征及总体生存率之间的关系。结果胃癌及癌旁正常组织中LETM1的阳性表达率分别为59.65%和15.78%( P< 0.05),且与肿瘤的分化程度( P =0.030)、临床TNM分期( P =0.003)及淋巴结转移( P =0.033)密切相关。预后结果分析显示, LETM1高表达的胃癌患者的3年总体生存率明显低于阴性表达者(χ^2=6.097, P< 0.05)。LETM1的表达水平、临床TNM分期、病理分化程度以及是否淋巴结转移均是胃癌患者预后的独立影响因素,LETM1表达水平高、临床分期晚、分化程度差、淋巴结转移阳性均可导致患者预后不良。结论 LETM1的异常表达与胃癌的发生发展密切相关,可将其作为判断临床预后的新型生物标志物。
基金supported by grants from the National Natural Science Foundation of China(No.81172545)the Chongqing Science and Technology Commission,China(No.cstc2020jcyj-msxmX0113).
文摘Osteosarcoma is a differentiation-deficient disease,and despite the unique advan-tages and great potential of differentiation therapy,there are only a few known differentia-tion inducers,and little research has been done on their targets.Cell differentiation is associated with an increase in mitochondrial content and activity.The metabolism of some tu-mor cells is characterized by impaired oxidative phosphorylation,as well as up-regulation of aerobic glycolysis and pentose phosphate pathways.Leucine-containing zipper and EF-hand transmembrane protein 1(LETM1)is involved in the maintenance of mitochondrial morphology and is closely associated with tumorigenesis and progression,as well as cancer cell stemness.We found that MG63 and 143B osteosarcoma cells overexpress LETM1 and exhibit abnormalities in mitochondrial structure and function.Knockdown of LETM1 partially restored the mitochon-drial structure and function,inhibited the pentose phosphate pathway,promoted oxidative phosphorylation,and led to osteogenic differentiation.It also inhibited spheroid cell forma-tion,proliferation,migration,and invasion in an in vitro model.When LETM1 was knocked down in vivo,there was reduced tumor formation and lung metastasis.These data suggest that mitochondria are aberrant in LETM1-overexpressing osteosarcoma cells,and knockdown of LETM1 partially restores the mitochondrial structure and function,inhibits the pentose phosphate pathway,promotes oxidative phosphorylation,and increases osteogenic differentiation,thereby reducing malignant biological behavior of the cells.
