染色质开放状态对食管癌相关通路影响及关键基因分析

Effects of Chromatin Opening Status on Pathways Associated with Esophageal Cancer and Analysis of Key Genes

目的:探讨染色质开放状态对食管癌相关通路的影响及对关键基因进行分析。方法:从癌症基因组图谱(TCGA)数据库下载食管癌染色质开放性高通量测序(ATAC-seq)数据,使用R4.2.1对2组数据分别进行基因注释,并进行KEGG通路富集分析与GO功能富集分析;对食管癌RNA-seq数据进行差异分析,筛选出与染色质开放状态相关性较高的2个基因ARL5B和RUNX1,并绘制KM生存曲线;对ARL5B、RUNX1进行单因素与多因素COX分析。结果:食管癌中ATAC-seq数据的峰值距离转录起始位点≤1 kb、1~2 kb、2~3 kb所占百分比分别为32.59%、6%、4.41%,位于远端基因间区的峰值占27.15%,这种现象和染色质开放区域的分布相一致。染色质开放区峰值绝大多数存在于转录起始位点附近,符合染色质开放性的特点。KEGG和GO功能分析结果显示,注释基因在Rap1信号通路、Hippo信号通路、ErbB信号通路、mTOR信号通路等明显富集。ARL5B高表达的食管癌患者预后较差(P<0.05),RUNX1高表达的食管癌患者预后较好(P<0.05)。结论:染色质开放状态在调节食管癌的发生和发展方面发挥重要作用,ARL5B、RUNX1基因可能成为食管癌的治疗靶点和预后指标。

Objective:To explore the effect of chromatin openness status on esophageal cancer-related pathways and to analyze the key genes.Methods:Based on the chromatin openness high-throughput sequencing(ATAC-seq)data and transcriptome sequen-cing(RNA-seq)data downloaded from the TCGA database,both sets of data were annotated using R4.2.1,and KEGG pathway enrichment analysis with GO functional enrichment analysis was performed.Differential analysis was performed on RNA-seq data of the esophageal cancer,ARL5B and RUNX1 genes that were highly correlated with chromatin open status were screened,and the KM survival curve was plotted.Univariate and multivariate COX analysis was performed for ARL5B and RUNX1.Results:The percenta-ges of ATAC-seq data in esophageal cancer with peaks≤1 kb,1~2 kb,and 2~3 kb away from the transcription start site were 32.59%,6.00%,4.41%,respectively,and peaks located in the distal intergenic region accounted for 27.15%,which was consistent with the distribution of chromatin open regions.The vast majority of the chromatin open region peaks existed near transcription start sites,which was also consistent with the characteristics of chromatin openness.The results of KEGG and GO functional analyses showed that the annotated genes were significantly enriched in the Rap1 signaling pathway,Hippo signaling pathway,ErbB signaling pathway,mTOR signaling pathway,etc.The prognosis of esophageal cancer patients with high expression of ARL5B was poorer(P<0.05).The prognosis of esophageal cancer patients with high expression of RUNX1 was better(P<0.05).Conclusion:Chro-matin openness plays an important role in regulating the functions related to the occurrence and development of esophageal cancer,and ARL5B and RUNX1 may become therapeutic targets and prognostic indicators for esophageal cancer.