基于泛癌分析法的WASH基因亚型在肿瘤中的意义

Significance of WASH genetic subtypes in tumors based on pan-cancer analysis

目的:利用泛癌分析法初步探讨WASH2P、WASH3P、WASH4P、WASH6P、WASH7P、WASH8P、WASH9P在33种癌症中的意义。方法:从TCGA数据库下载33种癌症的转录组数据,利用Perl软件提取WASH2P、WASH3P、WASH4P、WASH6P、WASH7P、WASH8P、WASH9P在33种癌症中的表达水平。采用R软件的limma包鉴定部分肿瘤类型(癌旁样本≥5)中的差异基因,结合TCGA的临床信息,利用Kaplan-Meier和Cox分析WASH亚型的临床预后意义。通过ESTIMATE包探讨WASH与肿瘤免疫浸润微环境的相关性,结合TCGA数据,分析WASH亚型与干细胞指数、免疫亚型间的相关性。最后,分析WASH亚型与单个肿瘤的免疫亚型、干细胞指数、临床分期及肿瘤免疫浸润微环境间的关系。结果:WASH3P和WASH8P在33种癌症类型中总体表达水平相对其他亚型呈高表达。WASH基因亚型在大部分肿瘤中(癌旁样本≥5)显著差异表达,共同协作影响肿瘤进展。生存分析显示其与多种癌症的预后相关(P<0.05)。在大部分肿瘤中,WASH基因亚型与肿瘤干细胞指数呈正相关。WASH基因亚型在C6免疫亚型中低表达,在C1~C4中等水平表达,在C5中高表达。WASH基因亚型表达水平越高,免疫成分、基质成分越少。单肿瘤分析结果显示,在部分单个肿瘤中,WASH基因亚型与TNM分期、免疫亚型、肿瘤微环境、干细胞指数存在相关性。结论:WASH在肿瘤发生发展中扮演重要角色,有望成为多种类型癌症的临床评估标志物。

Objective:To preliminarily explore the significance of WASH2P,WASH3P,WASH4P,WASH6P,WASH7P,WASH8P,WASH9P in 33 cancers using pan-cancer analysis.Methods:Transcriptome data of 33 cancers were downloaded from TCGA database,and expression levels of WASH2P,WASH3P,WASH4P,WASH6P,WASH7P,WASH8P,WASH9P in 33 cancers were extracted using Perl software.Differential genes in selected tumor types(paraneoplastic samples≥5)were identified using the limma package of R software,and the significance of WASH subtypes in relation to clinical prognosis of various tumors was analyzed using Kaplan-Meier and Cox in combination with clinical information from TCGA.The correlation between WASH and tumor immune infiltration microenvironment was explored by ESTIMATE package,and the correlation between WASH subtypes and stem cell indices and immune subtypes was analyzed by TCGA data.Finally,the relationships between WASH subtypes in individual tumor and immune subtypes,stem cell index,clinical stage and tumor immune infiltration microenvironment were analyzed.Results:Overall expression levels of WASH3P and WASH8P were higher in 33 cancer types than in other subtypes.WASH genotypes were significantly different expressed in most tumors(≥5 in paraneoplastic samples)and worked together to influence tumor progression.Survival analysis showed an association with prognosis in multiple tumors(P<0.05).In most tumors,WASH genotypes were positively correlated with tumor stem cell index.WASH genotypes were lowly expressed in C6 immune subtypes,moderately expressed in C1~C4 and highly expressed in C5.The higher the expression level of WASH genotypes,the lower the immune components and stromal components.results of single tumor analysis showed that in some tumors,WASH gene subtypes were correlated with TNM stage,immune subtype,tumor microenvironment and stem cell index.Conclusion:WASH plays an important role in tumor development and is expected to be a marker for clinical index assessment in many types of cancer.