基于TCGA数据库分析ASPM在肺腺癌中的表达及临床意义

目的：探讨异常纺锤体样小头畸形相关基因（ASPM）在肺腺癌中的表达水平，及其与患者临床病理指标和预后的关系。方法：从癌症基因组图谱（TCGA）数据库下载肺腺癌组织和癌旁组织mRNA表达水平和临床病例资料，比较ASPM mRNA在癌组织和癌旁组织中的表达差异，统计学分析ASPM表达水平与肺腺癌患者临床病理指标及预后关系。通过R语言ballgown和ggplot包筛选高低表达ASPM组间差异基因并绘制火山图；利用DAVID工具对差异基因进行GO分析，采用GSEA预测ASPM可能调控的信号通路；STRING和Cytoscape分析关键基因及差异表达基因间的相互作用。结果：ASPM mRNA在肺腺癌中表达水平显著高于癌旁组织（P < 0.05）；ASPM表达水平与生存期相关，高表达ASPM肺腺癌患者预后较差（P < 0.05），是肺腺癌患者预后的独立危险因素，R语言ballgown包筛选出ASPM高低表达组间的差异表达基因共183个，差异表达基因富集到生物过程（BP）、细胞组分（CC）、分子功能（MF）在3个类别共19个亚类和18条KEGG通路；Cytoscape软件发现4个枢纽蛋白。结论：ASPM mRNA在肺腺癌患者中呈高表达且高表达组预后差，可作为判断肺腺癌预后的标志物。

Expression and clinical significance of ASPM in lung adenocarcinoma according to the TCGA database

OBJECTIVE: Based on the cancer genome map (TCGA) database,associations between expression of abnormal spindle head malformation associated gene (ASPM) in lung adenocarcinoma and clinicopathological parameters were investigated. METHODS: The TCGA data on mRNA expression,and clinical characteristics of lung adenocarcinoma tissues and adjacent tissues were retrieved. The differences of ASPM mRNA expression in cancer and adjacent tissues were compared,and the relationship between ASPM expression level and clinicopathological parameters and prognosis of lung adenocarcinoma patients was statistically analyzed. Through R language ballgown and ggplot package,the differentially expressed genes between ASPM groups and drew volcano maps were screened. The David tools were used to analyze the differential genes,and GSEA was used to predict possible signal pathways which could be regulated by ASPM. String and Cytoscape were used to analyze key genes and interactions among differentially expressed genes. RESULTS: The expression level of ASPM mRNA in lung adenocarcinoma was significantly higher than that in adjacent tissues. In addition,the expression level of ASPM was correlated with survival time. The prognosis of patients with lung adenocarcinoma having high expression of ASPM was poor. This was also an independent risk factor for prognosis of lung adenocarcinoma patients. There were 183 differentially expressed genes between the ASPM high and low expression groups. The differentially expressed genes were enriched in biological process (BP),cell component (CC) and molecular function (MF) in three categories,including 19 subclasses and 18 KEGG pathways. Four key proteins were found by the Cytoscape software. CONCLUSION: ASPM mRNA was highly expressed in patients with lung adenocarcinoma and prognosis for the high expression group was poor. Our observations can be used as prognostic markers of lung adenocarcinoma.