利用GEO结肠癌芯片数据分析FOXC1及其相关基因的表达与意义

The expression and the clinical significance of FOXC1 in colon cancer based on genome microarray of GEO database

目的 探讨叉头框C1(forkhead box C1,FOXC1)在结肠癌的表达水平与临床病理特征及预后的关系,并分析预测与其表达密切相关的基因及其参与的生物过程。方法 利用高通量基因表达(Gene expression omnibus,GEO)数据库中结肠癌基因芯片数据分析FOXC1与临床病理特征及预后的相关性,采用R2平台,筛选出与FOXC1表达显著相关的基因进行基因本体(Gene Ontology,GO)和京都基因与基因组百科全书通路分析(kyoto encyclopedia of genes and genomes,KEGG)通路分析。结果 FOXC1的表达与肿瘤分化程度有关(χ2=7.919,P=0.019)。Kaplan-Meier法分析显示FOXC1的表达与患者的总生存期有相关性(P=0.045)。采用R2平台检测出与FOXC1表达显著相关基因共608个(其中正相关387个、负相关221个),对GO及KEGG通路分析后发现FOXC1高表达的肿瘤样本富集到其中564相关基因,主要涉及到血管生成、细胞增生、凋亡、细胞粘附、蛋白磷酸化信号传导、转录因子结合和上皮间质转化等多个肿瘤发生、发展过程。肿瘤信号通路主要涉及Wnt信号通路。结论 FOXC1表达在结肠癌中是一种不良预后因素,可作为判断预后的标志物。FOXC1表达相关的基因参与了多个结肠癌生物过程和信号通路,可为结肠癌分子标志物的深入研究提供参考。

Objective To investigate the relationship between expression of forkhead box C1(FOXC1)and clinicopathological and survival parameters in colon cancer,and predict the related genes and signaling pathways.Methods FOXC1 expression and clinicopathological information were downloaded from genome microarray of gene expression omnibus(GEO)database.The correlation between FOXC1 expression and clinicopathological factors and prognosis was analyzed.The R2 platform was used to search the genes associated with a significant expression with FOXC1.The gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were performed.Results There was a significant correlation between the expression of FOXC1 and tumor differentiation(χ2=7.919,P=0.019).High expression of FOXC1 indicated poor prognosis(P=0.045).In total,608 genes were identified which were associated with a significant expression with FOXC1(387 up-regulated genes and 221 down-regulated genes).GO analysis results showed that these genes were significantly enriched in biological processes,including angiogenesis,cell proliferation,cell apoptosis,cell adhesion,transcription factor binding,and epithelial to mesenchymal transition etc.The pathway analysis showed that these genes were mainly involved in Wnt signaling pathway.Conclusions The expression of FOXC1 indicates poor prognosis of colon cancer and can be used as a potential prognostic marker.The related genes set of FOXC1 were enriched in multiple biological processes and signaling pathways.This study provides guidance for the further study in colon cancer.