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应用生物信息学分析确定PLK4是乳腺癌的关键预后基因

Identification of PLK4 as a key prognostic gene in breast cancer by bioinformatics analysis

    摘要
  • 摘要:
      目的  应用生物信息学分析探讨Polo样激酶4（PLK4）在乳腺癌中的生物学作用、预后价值和对局部免疫微环境的影响。
      方法  通过Oncomine数据库挖掘PLK4在多种肿瘤中的表达水平；使用GEPIA数据库及HPA数据库检索PLK4在乳腺癌组织与正常组织中的表达差异；分别通过UALCAN数据库及TIMER数据库分析PLK4表达水平与乳腺癌患者临床特点及免疫浸润的相关性；采用K-M Plotter数据库评估PLK4在乳腺癌中的预后价值。应用Coexpedia数据库构建PLK4在乳腺癌中的共表达基因网络，并通过DAVID数据库对PLK4及其关键基因进行功能分析。
      结果  乳腺癌组织中，PLK4 mRNA和蛋白表达较正常乳腺组织均上调，特别是在P53突变和三阴性乳腺癌中差异更为显著（P < 0.05），且预示着更差的预后。PLK4在乳腺癌免疫微环境中与免疫细胞的表达呈正相关。筛选出PLK4的25个关键基因，即TPX2、CCNB2、CCNB1、BIRC5、CDC20和FOXM1等基因，其生物学功能主要与细胞分裂、细胞周期、细胞增殖和泛素化修饰等相关。KEGG通路富集分析表明，PLK4与P53信号通路、FoxO信号通路、MAPK信号通路和PI3K-Akt信号通路等相关。
      结论  PLK4在乳腺癌组织中呈高表达可提示患者不良预后，其影响乳腺癌局部免疫微环境，在一定程度上表现为癌基因的特性，推测其可作为乳腺癌治疗疗效的预测指标，有望成为乳腺癌临床诊疗的新靶点。

     

    Abstract:
      Objective  To explore the biological role and prognostic value of Polo-like kinase 4 (PLK4) in breast cancer and its influence on local immune microenvironment by bioinformatics analysis.
      Methods  The expression levels of PLK4 in a variety of tumors were mined through the Oncomine database. The differences in PLK4 expression in breast cancer tissues and normal tissues were retrieved by the GEPIA database and the HPA database. The correlations between PLK4 expression levels and clinical characters as well as immune infiltration in breast cancer patients were analyzed by the UALCAN database and the TIMER database respectively. The K-M plotter database was used to evaluate the prognostic value of PLK4 in breast cancer. Coexpedia database was used to construct the co-expressed gene network of PLK4 in breast cancer, and the functions of PLK4 and its key genes were analyzed by David database.
      Results  Both PLK4 mRNA and protein expression were significantly up-regulated in breast cancer tissues, especially in differences of P53 mutant and triple-negative breast cancers (P < 0.05), and high PLK4 expression indicated a worse prognosis. PLK4 was positively correlated with immune cell expression in the immune microenvironment of breast cancer. Twenty-five key genes of PLK4 were screened, including TPX2, CCNB2, CCNB1, BIRC5, CDC20, FOXM1 and etc, and their biological functions were mainly correlated with cell division, cell cycle, cell proliferation, ubiquitination modification and etc. KEGG pathway enrichment analysis showed that PLK4 was associated with P53 signaling pathway, FoxO signaling pathway, MAPK signaling pathway, PI3K-Akt signaling pathway, etc.
      Conclusion  The high expression of PLK4 in breast cancer tissues may indicate a poor prognosis, and it affects the immune microenvironment of breast cancer and shows the characteristics of oncogenes to a certain extent, so it might be used as a predictive indicator for the treatment of breast cancer, and is expected to become a new target for clinical diagnosis and treatment for breast cancer.

     

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