摘要
目的:利用生物信息学技术筛选与结肠癌发展及预后密切相关的潜在关键基因。方法:访问癌症基因组图谱(TCGA)并下载结肠癌患者的RNA表达数据和临床信息。利用R软件筛选结肠癌差异表达基因(DEGs)并对其进行KEGG通路富集分析,筛选在Wnt信号通路中显著富集的差异表达基因(DEGs)。利用STRING数据库构建蛋白质相互作用网络(PPI)并筛选Wnt通路连接度排名前10位的基因。运用Kaplan-Meier方法对筛选出的基因进行生存曲线评估,获取与结肠癌患者预后相关的关键基因。利用“ggpubr”包对关键基因与临床病理特征的相关关系进行分析并绘制箱线图。通过TIMER2.0网站(http://timer.cistrome.org/)、GEPIA数据库(http://gepia.cancer-pkucn/)分析关键基因在不同肿瘤组织和正常组织中的表达情况,基因相关性以及免疫浸润分析。结果:共鉴定出33个显著富集于Wnt信号通路的DEGs,其中连接度最高的前10个基因为WNT3A、AXIN2、DKK1、LEF1、WNT3、WNT11、WNT7B、DKK4、WIF1和WNT2。生存分析表明,WNT11高表达组患者的生存期显著低于低表达组(P<0.05),提示其预后不良。临床病理相关分析结果显示,WNT11表达与结肠癌患者的临床分期、远处转移状态以及淋巴结转移状态具有显著差异(P<0.05)。泛癌分析发现,WNT11在结肠癌、直肠腺癌、食管癌肿瘤组织中表达高于正常组织(P<0.05),在乳腺癌、肾癌、肺癌、嗜铬细胞瘤、甲状腺癌肿瘤组织中表达低于正常组织(P<0.05)。基因相关性分析显示,WNT11与LEF1、AXIN2、WIF1、WNT2、WNT3表达呈正相关(P<0.05)。免疫浸润分析发现,结肠癌中WNT11的表达水平与CD4+T淋巴细胞以及癌症相关成纤维细胞浸润程度呈正相关关系(P<0.05),与CD8+T淋巴细胞浸润程度呈显著负相关关系(P<0.05)。结论:WNT11在结肠癌肿瘤中呈高表达,其高表达与临床病理特征相关且预后较差,为探索结肠癌的发生发展机制及预后评估开辟了新的研究路径。
Objective:Potential key genes closely associated with colon cancer progression and prognosis are screened using bioinformatics techniques.Methods:Transcriptomic data and clinicaldata were downloaded from The Cancer Genome Atlas(TCGA)database.Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis was performed on differentially expressed genes by R software,to obtain differentially expressed genes(DEGs)significantly enriched in the WNT signalling pathway.The proteinprotein interaction(PPI)network was plotted with STRING database,and the top 10 hub genes were then screened from the PPI network.Survival curve analysis was conducted on the screened genes using the Kaplan-Meier method to identify key genes associated with colon cancer patient prognosis.The"ggpubr"package was used to analyse the correlation of key genes with clinicopathological features and to draw box plots.The expression of key genes in different tumor tissues and normal tissues,gene correlation and immune infiltration were analyzed through TIMER2.0,GEPIA database.Results:A total of 33 differentially expressed genes(DEGs)significantly enriched in the Wnt signaling pathway were identified.The top 10 genes with the highest connectivity are WNT3A,AXIN2,DKK1,LEF1,WNT3,WNT11,WNT7B,DKK4,WIF1,and WNT2.Survival analysis showed that patients in the WNT11 high-expression group had a significantly lower survival than those in the low expression group(P<0.05)and had a worse prognosis.Clinicopathological correlation analysis showed that there was a significant difference between WNT11 expression and clinical stage,distant metastasis status and lymph node metastasis status of colon cancer patients(P<0.05).Pan-cancer analysis revealed that WNT11 expression was higher than normal tissue in colon,rectal adenocarcinoma,and oesophageal cancer tumour tissues(P<0.05),and lower than normal tssue in breast,kidney,lung,pheochromocytoma,and thyroid cancer tumour tissues(P<0.05):Gene correlation analysis showed that WNT11 was positively correlated with the expression of LEF1,AXIN2,WIF1,WNT2 and WNT3(P<0.05).Immune infiltration analysis revealed that the expression level of WNT11 in colon cancer was positively correlated with the degree of infltration of CD4+T cells and cancer-associated fibroblasts(P<0.05)and negatively correlated with the degree of infiltration of CD8+T cells(P<0.05).Conclusion:WNT11 was highly expressed in colon cancer tumours,and its high expression was correlated with clinicopathological features and poor prognosis,which opens up new research paths for exploring the mechanisms of colon cancer development and prognostic assessment.
作者
甄秋来
马洪波
鲍杰
石海燕
ZHEN Qiu-lai;MA Hong-bo;BAO Jie(Department of blood transfusion,Zichuan District Hospital,Shandong Zibo 255100)
出处
《医学检验与临床》
2025年第4期1-8,共8页
Medical Laboratory Science and Clinics
基金
淄博市医药卫生科研项目,项目编号:20230303016。
