肝癌相关基因表达谱分析及TOP2A表达的临床意义

Identification of key pathways and genes in hepatocellular carcinoma and the clinical significance of gene TOP2A

目的探讨肝细胞性肝癌(HCC)相关基因的差异表达、富集通路和蛋白互作网络,分析差异表达基因与HCC预后的关系。方法分析TCGA数据库中HCC相关RNAseq数据,筛选差异表达基因,明确基因富集的GO和KEGG通路,构建蛋白互作网络,找到核心蛋白,通过生存分析,明确核心基因与HCC预后的关系。结果通过纳入标准筛选268个差异表达基因,显著富集在GO:mitotic nuclear division(P<0.001),cell division(P<0.001)和negative regulation of growth(P<0.001)及KEGG通路(hsa04110:Cell cycle)(P<0.001),均与细胞分裂与增殖密切相关。通过构建蛋白互作网络,筛选核心基因TOP2A,并在临床样本中得到验证(P<0.001)。生存分析显示,TOP2A的表达量与总体生存时间显著负相关(P=0.002)。结论 TCGA高通量数据分析是筛选肿瘤预后靶点的有效途径,TOP2A的高表达是肝细胞性肝癌预后的不良因素。

Objective To investigate the differentially expressed genes（DEGs） associated with hepatocellular carcinoma（HCC）, and to evaluate the relationship between DEGs and prognosis of HCC. Methods The RNAseq data related to HCC in TCGA database were analyzed to screen DEGs. Then significantly enriched GO and KEGG pathway would be identified, and the hub genes be found with protein-protein interaction network constructed. Hereafter, survival analysis was performed for the candidate hub gene. Results A total of 268 DEGs were screened and significantly enriched in GO： mitotic nuclear division（P〈0.001）, cell division（P〈0.001） and negative regulation of growth（P〈0.001） and KEGG pathway：（hsa04110：Cell cycle）（P〈0.001）. TOP2 Awas selected as a candidate hub gene with protein interaction network, which was verified by clinical samples（P〈0.001）. Survival analysis showed a significantly negative correlation between TOP2 A expression and overall survival（P=0.002）. Conclusion High-throughput TCGA data analysis is an effective way to screen the molecular markers of tumor. The high expression of TOP2 A is the poor prognostic factor of HCC.