基于生物信息学分析Wnt家族基因在实体肿瘤中的表达及其相关机制

Expression and potential molecular mechanisms of Wnt in solid tumor based on bioinformatics

目的探讨Wnt家族基因在实体肿瘤中的表达情况及其相关分子机制。方法利用Oncomine、UALCAN在线数据库对Wnt家族基因在各实体肿瘤中的表达分析验证,cBioPortal进行基因变异分析,TIMER数据库进行基因表达与免疫细胞浸润相关性分析。结果Wnt家族基因在实体肿瘤尤其是消化系统肿瘤中存在显著差异表达。在结肠癌中,Wnt2、Wnt3、Wnt5a及Wnt11表达显著上调,而Wnt2b、Wnt5b、Wnt10及Wnt13为表达下调基因。在食管癌中,Wnt2b、Wnt3、Wnt3a、Wnt4、Wnt5a、Wnt13的表达普遍下调,而在相关胃癌研究中提示Wnt2、Wnt4、Wnt5a表达上调。错义突变、基因扩增及深缺失是Wnt2、Wnt2b、Wnt3、Wnt5a、Wnt5b及Wnt11基因在结肠癌中发生基因变异的主要原因。在结肠癌中,Wnt2b、Wnt5b表达与CD4+T细胞浸润呈正相关;Wnt2、Wnt3、Wnt5a及Wnt11表达与CD4+T细胞、巨噬细胞浸润呈正相关;Wnt2、Wnt5a的表达与肿瘤纯度呈负相关;Wnt2、Wnt5a表达与CD8+T细胞及树突状细胞浸润呈正相关;Wnt3、Wnt11表达与B细胞、CD8+T细胞浸润呈负相关;Wnt2、Wnt3、Wnt5a表达与中性粒细胞浸润呈正相关。结论Wnt家族基因在实体肿瘤特别是肠道肿瘤中存在显著差异表达,Wnt2、Wnt2b、Wnt3、Wnt5a、Wnt5b、Wnt11等基因在肠癌中表达与错义突变、基因扩增及深缺失有关,并且与免疫细胞浸润存在一定相关性。

Objective To investigate the expression and prospective molecular mechanisms of Wnt family member genes in solid tumor.Methods Assessment of the expression of Wnt family member genes by using the tools included the Oncomine and UALCAN online database.Furthermore,analysis of gene variation was performed on the cBioportal online tool,and TIMER database was applied to search for a correlation of Wnt gene expression with tumor purity and the abundance of immune infiltrates in colon adenocarcinoma.Results The Wnt family genes were differentially expressed in the solid tumor,especially in the tumors of digestive system.The expression levels of Wnt2,Wnt2b,Wnt3,Wnt5a,Wnt5b,Wnt11 were correlated to gene mutations and copy number variations.In colorectal cancer,the expression levels of Wnt2,Wnt3,Wnt5a and Wnt11 were significantly upregulated,while Wnt2b,Wnt5b,Wnt10 and Wnt13 were downregulated genes.In esophageal cancer,the expression levels of Wnt2b,Wnt3,Wnt3a,Wnt4,Wnt5a,Wnt13 were generally down-regulated,while Wnt2,Wnt4,Wnt5a were overexpressed in gastric cancer.In colorectal cancer,significant positive correlation was observed between Wnt2,Wnt3,Wnt5a,Wnt11 expression and high infiltration of CD4+T cell and Macrophage.The percentage of infiltrating B cells and CD8+T cells was negatively correlated with Wnt3,Wnt11 expression.In addition,the expression levels of Wnt2b and Wnt5b were positively correlated to CD4+T cell infiltration levels,while,expression levels of Wnt2,Wnt3,Wnt5a showed positive correlation with the level of neutrophil infiltration.Interestingly,Wnt2 and Wnt5a expression indicated positive correlation with CD8+T cells and dendritic cell,negative correlation with tumor purity.Conclusion Wnt family genes with statistically significant differential expression in the solid tumor,especially in the esophageal,gastric and colorectal cancer.Amplification,deep deletion and missense mutation are the main causes of genetic alteration in Wnt2,Wnt2b,Wnt3,Wnt5a,Wnt5b and Wnt11.The expression levels of Wnt2,Wnt2b,Wnt3,Wnt5a,Wnt5b,Wnt11 are correlated to various immune cells infiltration levels.