基于TCGA分析HAVCR2基因在食管癌中表达及其与免疫微环境的关系

The expression of HAVCR2 gene in esophageal cancer and its relationship with immune microenvironment based on TCGA

目的利用TCGA数据库中转录组数据分析HAVCR2基因在食管癌中的表达及其与临床特征、免疫微环境的关系,为改进食管癌的治疗方法提供一定的理论依据。方法从TCGA公共数据库中获取食管癌组织及正常食管黏膜组织的RNA测序数据和食管癌组织所对应的临床数据。通过非参数检验分析HAVCR2在食管癌组织和正常食管组织的表达差异。根据TCGA-ESCA数据库中总生存期数据绘制HAVCR2高低表达组的Kaplan-Meier生存曲线,并进行Log-rank检验。通过单因素Cox回归分析初步找出影响食管癌患者生存状态的主要因素。最后评估HAVCR2表达与肿瘤免疫微环境之间的关系。结果HAVCR2基因在食管癌组织中表达上调,但HAVCR2基因表达与食管癌患者的总生存期无关,不能够作为食管癌的预后因子。单因素Cox回归分析显示,有淋巴结转移的食管癌患者预后较差。在肿瘤微环境的分析中,HAVCR2高表达的食管癌中免疫成分和基质成分更高,但肿瘤纯度较低。HAVCR2高表达时,肿瘤微环境中免疫细胞种类及数量增多,免疫功能可能处于激活状态。高低表达组之间免疫细胞差异和免疫检查点基因表达差异显著。富集分析显示差异表达基因主要富集于与免疫相关的通路。结论HAVCR2基因在食管癌样本中表达高于正常食管黏膜组织,与临床特征的关系并不显著,在肿瘤免疫微环境中发挥作用,表明HAVCR2基因可以为食管癌的治疗和诊断提供一定的思路。

Objective To analyze the expression of HAVCR2 gene in esophageal cancer(ESCA)and its relationship with clinical characteristics and immune microenvironment using the transcriptome data in the TCGA database,so as to provide a theoretical basis for improving the treatment of ESCA.Methods The RNA sequencing data of esophageal cancer tissues and normal esophageal mucosa tissues and the clinical data corresponding to ESCA tissues were obtained from the TCGA public database.The expression differences of HAVCR2 in esophageal cancer tissues and normal esophageal tissues were analyzed by nonparametric test.The Kaplan-Meier survival curves of the HAVCR2 high and low expression groups were drawn according to the overall survival data in the TCGA-ESCA database,and the Log-rank test was performed.The main factors affecting the survival status of ESCA patients were preliminarily identified by univariate Cox regression analysis.Finally,the relationship between the expression of HAVCR2 and the tumor immune microenvironment was explored.Results The expression of HAVCR2 gene was upregulated in ESCA,but HAVCR2 gene expression was not associated with the overall survival of patients with ESCA,and could not be used as a prognostic factor for ESCA.Univariate Cox regression analysis showed that patients with ESCA with lymph node metastasis had a poor prognosis.In the analysis of the tumor microenvironment,ESCA with high HAVCR2 expression had higher immune and stromal components,but lower tumor purity.When HAVCR2 was highly expressed,the types and numbers of immune cells in the tumor microenvironment increased,and the immune function might be activated.Differences in immune cell and immune checkpoint gene expression between high and low expression groups were significant.Enrichment analysis showed that differentially expressed genes were mainly enriched in immune-related pathways.Conclusion The expression of HAVCR2 gene in esophageal cancer samples is higher than that of normal esophageal mucosa,and the relationship with clinical characteristics is not significant.It plays a role in the tumor immune microenvironment,indicating that HAVCR2 gene can provide certain ideas for the treatment and diagnosis of esophageal cancer.