目的 探讨肝细胞肝癌(LIHC)中NDC1基因的表达水平及临床价值。方法 利用The Human Protein Atlas、GEPIA、TIMER数据库在线分析NDC1基因在健康人体各器官组织、正常肝组织和肝细胞肝癌组织中的表达情况。利用Kaplan-Meier Ploter和UALCA...目的 探讨肝细胞肝癌(LIHC)中NDC1基因的表达水平及临床价值。方法 利用The Human Protein Atlas、GEPIA、TIMER数据库在线分析NDC1基因在健康人体各器官组织、正常肝组织和肝细胞肝癌组织中的表达情况。利用Kaplan-Meier Ploter和UALCAN数据库的肝癌数据集在线分析患者NDC1表达与生存总周期的关系。通过STRING数据库在线检索NDC1的相关蛋白网络图,并进行功能注释和KEGG通路富集分析。通过TIMER数据库检测NDC1在肝癌中的免疫细胞的浸润水平以分析临床不良预后的相关性。结果 人体不同器官的NDC1 m RNA存在差异表达。与对照组相比,NDC1基因在乳腺癌、膀胱癌、结肠癌、胆管癌、肺鳞癌、肝癌的表达水平显著上升,且差异有显著统计学意义(P<0.001)。肝癌组织NDC1 m RNA的表达水平高于正常肝脏组织,肝癌组织中NDC1 m RNA表达水平明显上调,差异有统计学意义(P<0.05)。NDC1基因在正常肝组织中的表达水平为2.356(1.728~2.878)。根据病理分级,NDC1基因在1级肝癌组织中的表达水平为3.071 (2.475~4.981),在2级肝癌组织中的表达水平为3.69 (2.457~5.305),在3级肝癌组织中的表达水平为4.676 (2.745~6.874),在4级肝癌组织中的表达水平为4.586 (3.159~6.954),各级肝癌中NDC1的表达水平差异有显著统计学意义(P<0.01);根据肿瘤临床分期,NDC1基因在Ⅰ期肝癌组织中表达水平为3.323 (2.371~5.414),在Ⅱ期肝癌组织中表达水平为4.294 (2.704~7.496),在Ⅲ期肝癌组织中表达水平为4.684 (2.979~7.037),在Ⅳ期肝癌组织中表达水平为1.983 (1.801~2.669),肝癌Ⅰ、Ⅱ和Ⅲ期中NDC1基因的表达水平均显著高于正常组织(P<0.001),而肝癌Ⅱ期和Ⅲ期中的表达水平显著高于Ⅰ期,差异具有显著统计学意义(P<0.01);根据身体质量指数分组,在正常体质量的肝癌组织表达水平为3.62 (2.584~5.661),在超常体质量的肝癌组织表达水平为3.841 (2.098~6.056),在肥胖的肝癌组织表达水平为3.627 (2.504~5.182),在极度肥胖的肝癌组织表达水平为3.577 (2.359~4.909)。任何BMI患者的肝癌组织中NDC1的表达水平均显著高于正常肝脏组织,差异具有显著统计学意义(P<0.01)。NDC1与CDK1、CCNB1、CCNB2、SEH1L、NUP155、CDCA8等蛋白相关,NDC1 m RNA在肝癌免疫微环境中与CD8^(+)T细胞、CD4^(+)T细胞、T细胞、B细胞、中性粒细胞、单核细胞、巨噬细胞和骨髓细胞等免疫细胞中的表达呈正相关性(P<0.05)。结论 肝癌组织中NDC1基因呈现高表达水平,其表达水平与肝癌的发生、发展及预后密切相关,可能是肝癌潜在的预后生物学标志物及治疗靶标。展开更多
The mechanism by which chromosomes establish and maintain a dynamic coupling to microtubules for force generation during the complex motions of mitosis remains elusive. Equally challenging is an explanation for the ti...The mechanism by which chromosomes establish and maintain a dynamic coupling to microtubules for force generation during the complex motions of mitosis remains elusive. Equally challenging is an explanation for the timing of poleward, antipoleward, and oscillatory chromosome movements. The molecular cell biology paradigm requires that specific molecules, or molecular geometries, for force generation are necessary for chromosome motions. We propose here that the dynamics of mitotic chromosome motions are an emergent property of a changing intracellular pH in combination with electrostatic forces. We explain this mechanism within the context of Complexity Theory, based on the electrostatic properties of tubulin, known cellular electric charge distributions, and the dynamic instability of microtubules.展开更多
Recent experiments revealing possible nanoscale electrostatic interactions in force generation at kinetochores for chromosome motions have prompted speculation regarding possible models for interactions between positi...Recent experiments revealing possible nanoscale electrostatic interactions in force generation at kinetochores for chromosome motions have prompted speculation regarding possible models for interactions between positively charged molecules in kinetochores and negative charge on C-termini near the plus ends of microtubules. A clear picture of how kinetochores establish and maintain a dynamic coupling to microtubules for force generation during the complex motions of mitosis remains elusive. The molecular cell biology paradigm requires that specific molecules, or molecular geometries, for force generation be identified. However, it is possible to account for mitotic chromosome motions within a systems approach in terms of experimentally known cellular electric charge distributions interacting over nanometer distances.展开更多
文摘目的 探讨肝细胞肝癌(LIHC)中NDC1基因的表达水平及临床价值。方法 利用The Human Protein Atlas、GEPIA、TIMER数据库在线分析NDC1基因在健康人体各器官组织、正常肝组织和肝细胞肝癌组织中的表达情况。利用Kaplan-Meier Ploter和UALCAN数据库的肝癌数据集在线分析患者NDC1表达与生存总周期的关系。通过STRING数据库在线检索NDC1的相关蛋白网络图,并进行功能注释和KEGG通路富集分析。通过TIMER数据库检测NDC1在肝癌中的免疫细胞的浸润水平以分析临床不良预后的相关性。结果 人体不同器官的NDC1 m RNA存在差异表达。与对照组相比,NDC1基因在乳腺癌、膀胱癌、结肠癌、胆管癌、肺鳞癌、肝癌的表达水平显著上升,且差异有显著统计学意义(P<0.001)。肝癌组织NDC1 m RNA的表达水平高于正常肝脏组织,肝癌组织中NDC1 m RNA表达水平明显上调,差异有统计学意义(P<0.05)。NDC1基因在正常肝组织中的表达水平为2.356(1.728~2.878)。根据病理分级,NDC1基因在1级肝癌组织中的表达水平为3.071 (2.475~4.981),在2级肝癌组织中的表达水平为3.69 (2.457~5.305),在3级肝癌组织中的表达水平为4.676 (2.745~6.874),在4级肝癌组织中的表达水平为4.586 (3.159~6.954),各级肝癌中NDC1的表达水平差异有显著统计学意义(P<0.01);根据肿瘤临床分期,NDC1基因在Ⅰ期肝癌组织中表达水平为3.323 (2.371~5.414),在Ⅱ期肝癌组织中表达水平为4.294 (2.704~7.496),在Ⅲ期肝癌组织中表达水平为4.684 (2.979~7.037),在Ⅳ期肝癌组织中表达水平为1.983 (1.801~2.669),肝癌Ⅰ、Ⅱ和Ⅲ期中NDC1基因的表达水平均显著高于正常组织(P<0.001),而肝癌Ⅱ期和Ⅲ期中的表达水平显著高于Ⅰ期,差异具有显著统计学意义(P<0.01);根据身体质量指数分组,在正常体质量的肝癌组织表达水平为3.62 (2.584~5.661),在超常体质量的肝癌组织表达水平为3.841 (2.098~6.056),在肥胖的肝癌组织表达水平为3.627 (2.504~5.182),在极度肥胖的肝癌组织表达水平为3.577 (2.359~4.909)。任何BMI患者的肝癌组织中NDC1的表达水平均显著高于正常肝脏组织,差异具有显著统计学意义(P<0.01)。NDC1与CDK1、CCNB1、CCNB2、SEH1L、NUP155、CDCA8等蛋白相关,NDC1 m RNA在肝癌免疫微环境中与CD8^(+)T细胞、CD4^(+)T细胞、T细胞、B细胞、中性粒细胞、单核细胞、巨噬细胞和骨髓细胞等免疫细胞中的表达呈正相关性(P<0.05)。结论 肝癌组织中NDC1基因呈现高表达水平,其表达水平与肝癌的发生、发展及预后密切相关,可能是肝癌潜在的预后生物学标志物及治疗靶标。
文摘The mechanism by which chromosomes establish and maintain a dynamic coupling to microtubules for force generation during the complex motions of mitosis remains elusive. Equally challenging is an explanation for the timing of poleward, antipoleward, and oscillatory chromosome movements. The molecular cell biology paradigm requires that specific molecules, or molecular geometries, for force generation are necessary for chromosome motions. We propose here that the dynamics of mitotic chromosome motions are an emergent property of a changing intracellular pH in combination with electrostatic forces. We explain this mechanism within the context of Complexity Theory, based on the electrostatic properties of tubulin, known cellular electric charge distributions, and the dynamic instability of microtubules.
文摘Recent experiments revealing possible nanoscale electrostatic interactions in force generation at kinetochores for chromosome motions have prompted speculation regarding possible models for interactions between positively charged molecules in kinetochores and negative charge on C-termini near the plus ends of microtubules. A clear picture of how kinetochores establish and maintain a dynamic coupling to microtubules for force generation during the complex motions of mitosis remains elusive. The molecular cell biology paradigm requires that specific molecules, or molecular geometries, for force generation be identified. However, it is possible to account for mitotic chromosome motions within a systems approach in terms of experimentally known cellular electric charge distributions interacting over nanometer distances.
