KIF4A在乳腺癌中的功能分析及临床意义(1)
【摘要】 目的 研究KIF4A基因在乳腺癌中的表达情况，并探讨其可能的作用机制及表达差异与预后的关系。方法 从肿瘤基因组图谱(TCGA)数据库收集乳腺癌数据集，下载KIF4A基因表达谱资料，相对表达量的中位数为5.77，以5.77为节点将乳腺癌患者分为KIF4A高表达组与KIF4A低表达组，分析其与病例特征的关系;利用Kaplan?Meier Plotter分析KIF4A与乳腺癌患者预后的相关性。结果 KIF4A在乳腺癌組织中的表达明显高于正常乳腺组织及乳腺细胞(P<0.01)，KIF4A主要分布于细胞核和细胞骨架中，KEGG通路分析和GO功能分析显示KIF4A与细胞周期、RNA转运、P53信号通路、细胞分裂、端粒维持重组等功能有关。KIF4A与Ki67的表达高度正相关(P<0.001)，预后分析表明KIF4A表达越高，乳腺癌患者总生存时间和无复发生存时间更短(P<0.001)。KIF4A的表达与淋巴结阴性乳腺癌的总生存率具有负相关性(P<0.001)，而与淋巴结阳性乳腺癌的总生存率则不相关。结论 在乳腺癌中，KIF4A高表达并且和患者的预后相关，KIF4A在乳腺癌的发生中可能起着重要作用。
【关键词】 乳腺癌;功能分析;KIF4A;预后
【Abstract】 Objective To investigate the expression level of KIF4A gene in breast cancer，explore the potential mechanism and unravel the relationship between the expression difference and clinical prognosis. Methods Data sets of breast cancer patients were collected from The Cancer Genome Atlas (TCGA) database and the expression profile of KIF4A gene was downloaded. The median relative expression level was 5.77. All participants were divided into the high? and low?expression groups according to the value of 5.77. The relationship between KIF4A gene expression and clinical characteristics was analyzed. Kaplan?Meier plot was utilized to analyze the correlation between KIF4A gene and clinical prognosis of breast cancer patients. Results The expression level of KIF4A in the breast cancer tissues was significantly higher than that in the normal breast tissues and cells (P<0.01). KIF4A was mainly distributed in the nucleus and cytoskeleton. KEGG pathway analysis and GO function analysis demonstrated that KIF4A was associated with cell cycle，RNA transport，P53 signaling pathway，cell division，telomere maintenance and recombination，etc. The KIF4A was positively correlated with the expression of Ki67 (P<0.001). Prognostic analysis revealed that the higher the expression of KIF4A，the shorter the overall survival and recurrence?free survival time of breast cancer patients (P<0.001). The expression of KIF4A was negatively correlated with the overall survival rate of patients diagnosed with lymph node?negative breast cancer (P<0.001)，whereas it was not associated with that of their counterparts with lymph node?positive breast cancer. Conclusion KIF4A is highly expressed in breast cancer patients and is associated with clinical prognosis. KIF4A may play a pivotal role in the incidence of breast cancer.
【Key words】 Breast cancer;Functional analysis;KIF4A;Prognosis
乳腺癌是女性常见、病死率高的恶性肿瘤之一[1]。乳腺癌的发生与遗传、激素影响、生活方式等因素相关，但其具体发病机制尚未明确。乳腺癌的发生发展过程复杂，涉及多条信号通路[2]。其中驱动蛋白家族蛋白(KIF)作为在有丝分裂中沿着微管转运染色体的工具分子在乳腺癌的疾病进展中发挥着重要作用[3]。KIF是一类马达蛋白，利用ATP水解释放的能量，使其自身及转运的货物沿微管运动，参与细胞内物质运输、细胞的分裂并信号转导，其家族有14个发挥着不同功能的成员，其中KIF4A可在染色体收缩和有丝分裂的机械隔离中发挥作用[4]。研究表明，KIF4A与多种肿瘤的发生发展密切相关[5?9]。阿霉素可诱导乳腺癌细胞系凋亡，其机制可能涉及下调KIF4A进而导致DNA修复酶聚腺苷酸二磷酸核糖转移酶?1(PARP?1)上调[10]。但是对KIF4A基因在乳腺癌中的表达及具体机制仍未明确，在本研究中，笔者通过肿瘤基因组图谱TCGA数据库，研究KIF4A在乳腺癌中的表达及其对预后的影响，并分析其在乳腺癌中可能的生物功能，为进一步研究KIF4A在肿瘤发生发展中的作用机制提供线索和思路。, 百拇医药(吴珏堃 熊志勇)
【关键词】 乳腺癌;功能分析;KIF4A;预后
【Abstract】 Objective To investigate the expression level of KIF4A gene in breast cancer，explore the potential mechanism and unravel the relationship between the expression difference and clinical prognosis. Methods Data sets of breast cancer patients were collected from The Cancer Genome Atlas (TCGA) database and the expression profile of KIF4A gene was downloaded. The median relative expression level was 5.77. All participants were divided into the high? and low?expression groups according to the value of 5.77. The relationship between KIF4A gene expression and clinical characteristics was analyzed. Kaplan?Meier plot was utilized to analyze the correlation between KIF4A gene and clinical prognosis of breast cancer patients. Results The expression level of KIF4A in the breast cancer tissues was significantly higher than that in the normal breast tissues and cells (P<0.01). KIF4A was mainly distributed in the nucleus and cytoskeleton. KEGG pathway analysis and GO function analysis demonstrated that KIF4A was associated with cell cycle，RNA transport，P53 signaling pathway，cell division，telomere maintenance and recombination，etc. The KIF4A was positively correlated with the expression of Ki67 (P<0.001). Prognostic analysis revealed that the higher the expression of KIF4A，the shorter the overall survival and recurrence?free survival time of breast cancer patients (P<0.001). The expression of KIF4A was negatively correlated with the overall survival rate of patients diagnosed with lymph node?negative breast cancer (P<0.001)，whereas it was not associated with that of their counterparts with lymph node?positive breast cancer. Conclusion KIF4A is highly expressed in breast cancer patients and is associated with clinical prognosis. KIF4A may play a pivotal role in the incidence of breast cancer.
【Key words】 Breast cancer;Functional analysis;KIF4A;Prognosis
乳腺癌是女性常见、病死率高的恶性肿瘤之一[1]。乳腺癌的发生与遗传、激素影响、生活方式等因素相关，但其具体发病机制尚未明确。乳腺癌的发生发展过程复杂，涉及多条信号通路[2]。其中驱动蛋白家族蛋白(KIF)作为在有丝分裂中沿着微管转运染色体的工具分子在乳腺癌的疾病进展中发挥着重要作用[3]。KIF是一类马达蛋白，利用ATP水解释放的能量，使其自身及转运的货物沿微管运动，参与细胞内物质运输、细胞的分裂并信号转导，其家族有14个发挥着不同功能的成员，其中KIF4A可在染色体收缩和有丝分裂的机械隔离中发挥作用[4]。研究表明，KIF4A与多种肿瘤的发生发展密切相关[5?9]。阿霉素可诱导乳腺癌细胞系凋亡，其机制可能涉及下调KIF4A进而导致DNA修复酶聚腺苷酸二磷酸核糖转移酶?1(PARP?1)上调[10]。但是对KIF4A基因在乳腺癌中的表达及具体机制仍未明确，在本研究中，笔者通过肿瘤基因组图谱TCGA数据库，研究KIF4A在乳腺癌中的表达及其对预后的影响，并分析其在乳腺癌中可能的生物功能，为进一步研究KIF4A在肿瘤发生发展中的作用机制提供线索和思路。, 百拇医药(吴珏堃 熊志勇)
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