HOXC8在食管癌中的表达及富集分析

Expression and enrichment analysis of HOXC8 in esophageal cancer

目的探讨HOXC8在食管癌中的表达情况及其可能参与的信号通路。方法从癌症和肿瘤基因组图谱(TCGA)数据库中下载并预处理食管癌数据集的mRNA表达RNA-Seq数据及临床预后相关数据,进行差异表达基因分析,并绘制火山图和热图,对筛选出的差异表达基因进行可视化。以HOXC8表达量的中位数为界将食管癌患者分为高表达组和低表达组,使用Kaplan-Meier法进行生存分析。然后使用GSEA 4.0.1软件进行基因集富集分析,同时进行多GSEA富集分析的图形绘制。结果对161例食管癌组织和11例癌旁组织的mRNA表达数据进行差异表达分析后,共筛选出3454个差异表达基因,其中有2317个上调的基因和1137个下调的基因,聚类分析结果显示,差异表达可以把食管癌与癌旁组织有效区分开,说明上述差异表达结果具有很好的准确性。差异分析和配对差异分析结果显示,HOXC8在食管癌中显著高表达,与癌旁组织的差异具有统计学意义(t=5.333,P<0.001;t=3.101,P=0.007)。删除生存时间<30 d的样本后,共有107例样本,HOXC8高表达患者(n=54)的预后更差,中位生存时间为553 d(95%CI为396~710),HOXC8低表达患者(n=53)的中位生存时间为784 d(95%CI为62~1506),差异有统计学意义(χ2=4.153,P=0.042),提示HOXC8为癌基因。GSEA分析结果显示,HOXC8高表达样本富集了细胞周期、剪接体等相关基因集,而HOXC8低表达样本则富集了磷脂酰肌醇信号通路等相关基因集。结论HOXC8在食管癌中显著高表达,且HOXC8高表达的患者预后更差,其可能通过参与细胞周期、剪接体、磷脂酰肌醇信号通路等调节食管癌的发生发展。

Objective To investigate the expression of HOXC8 in esophageal cancer and its possible signaling pathway.Methods The RNA-Seq data of mRNA expression and clinical prognosis data of esophageal cancer dataset were downloaded and preprocessed from the TCGA(The Cancer Genome Atlas)database.The differentially expressed genes were analyzed,and the volcano map and heat map were drawn to visualize the screened differentially expressed genes.The patients with esophageal cancer were divided into high expression group and low expression group based on the median of HOXC8 expression,and survival analysis was performed using Kaplan-Meier method.GSEA 4.0.1 software was used for gene set enrichment analysis,and graphic analysis of multi-GSEA enrichment analysis was performed at the same time.Results After differential expression analysis of mRNA expression data of 161 esophageal cancer tissues and 11 paracancerous tissues,3454 differentially expressed genes were screened,including 2317 up-regulated genes and 1137 down-regulated genes.The results of cluster analysis showed that differential expression can effectively distinguish esophageal cancer from adjacent tissues,indicating that the above differential expression results had good accuracy.Difference analysis and paired difference analysis showed that HOXC8 was significantly overexpressed in esophageal cancer,and the differences with tissues adjacent to cancer were statistically significant(t=5.333,P<0.001;t=3.101,P=0.007).After removing samples with a survival time of less than 30 days,a total of 107 samples were used.The results showed that patients with high expression of HOXC8(n=54)had a worse prognosis,with a median survival time of 553 days(95%CI:396-710),and the median survival time of patients with low expression of HOXC8(n=53)was 784 days(95%CI:62-1506),with a statistically significant difference(χ2=4.153,P=0.042),suggesting that HOXC8 was an oncogene.The results of GSEA analysis showed that the samples with high expression of HOXC8 enriched the cell cycle,spliceosome and other related gene sets,while the samples with low expression of HOXC8 enriched the phosphatidylinositol signaling pathway and other related gene sets.Conclusion HOXC8 is significantly overexpressed in esophageal cancer,and patients with high expression of HOXC8 have a worse prognosis.It may regulate the occurrence and development of esophageal cancer through the involvement of cell cycle,spliceosome,phosphatidylinositol signaling pathway and other signaling pathways.