上皮-间充质转化过程导致结直肠癌远处转移的关键基因筛选和分析

Screening and analysis of critical genes in colorectal cancer leading to distant metastasis via the epithelial-mesenchymal transition process

目的本研究通过生物信息学方法确定通过上皮-间充质转化(EMT)调控影响结直肠癌远处转移的关键基因,并探究分子机制和预后。方法通过分析Enrichr数据库中的基因组,获得EMT和转移性结直肠癌之间共同表达的枢纽基因。基因表达谱数据动态分析(GEPIA)被用来分析识别关键基因。利用多个生物信息数据库公布的数据,分析关键基因在结直肠癌中的表达和功能富集。利用癌症基因组图谱(TCGA)和基因表达谱数据库(GEO)探讨关键基因与结直肠癌病理特征和预后之间的关系,并利用京都基因和基因组百科全书(KEGG)探究可能存在的通路及分子机制。结果两个关键基因P21活化激酶1(PAK1)和转化生长因β3(TGFB3),分析与预后及病理特征关系。结果显示,PAK1低表达组的总体生存率低于高表达组[风险比(HR)=0.641,P<0.05],TGFB3高表达组的总体生存率低于低表达组(HR=1.561 P<0.05)。TGFB3的表达水平与结直肠癌的M分期(t=6.314,P<0.05)、病理分期(t=4.368,P<0.05)和N分期(t=5.843,P<0.05)显著相关;PAK1高表达组与人种(t=2.367,P<0.05)、病理分期(t=1.540,P<0.05)、N分期(t=1.677,P<0.05)和M分期(t=7.561,P<0.05)显著相关。KEGG路径分析确定了PAK1和TGFB3靶基因分别在"细胞因子受体相互作用"和"肌动蛋白细胞骨架调节"中的起着关键作用。结论PAK1和TGFB3可能通过相关的分子机制影响结直肠癌的上皮-间充质转化,并与预后明显相关。

Objective To identify key genes that influence distant metastasis in colorectal cancer(CRC)through epithelial-mesenchymal transition(EMT)regulation and explore the associated molecular mechanisms and prognosis.Methods We obtained the hub genes co-expressed between EMT and metastatic colorectal cancer by analysing Enrichr’s gene sets.GEPIA was used to analyze modules and identify key genes.We analyzed the transcriptional expression and functional enrichment in CRC of key genes based on the data published in the following databases:UALCAN,Oncomine,Cancer Cell Line Encyclopedia,LinkedOmics,Metascape.The cancer genome atlas(TCGA)and gene expression omnibus(GEO)databases were used to explore relationships between key genes and pathological features and prognosis of CRC,and kyoto encyclopedia of genes and genomes(KEGG).Results There were 2 key genes(PAK1 and TGFB3)with prognostic and pathological features.The results showed that low expression of PAK1 was associated with poor prognosis(P<0.05),and high expression of TGFB3 was associated with poor prognosis(P<0.05).High expression of TGFB3 was significantly associated with M1(P<0.01),stage Ⅳ(P<0.01),and N2(P<0.01).The high expression of PAK1 was significantly associated with yellow race(P<0.05),stage Ⅰ(P<0.05),stage Ⅱ(P<0.05),N0(P<0.05)and M0(P<0.01).Genes closely related to changes in the TGFB3 and PAK1 key genes were screened,and KEGG pathway analysis identified positional relationships of PAK1 and TGFB3-associated genes in the cytokine receptor interaction and regulation of actin cytoskeleton,respectively.Conclusion PAK1 and TGFB3 may influence the EMT in CRC through related molecular mechanisms and are significantly associated with prognosis.