Snail基因mRNA与结肠癌患者预后的生物信息学分析

Expression of Snail in Colorectal Cancer,Related Signal Pathway and its Relationship with Prognosis

目的:探讨Snail在结直肠癌中的表达及其与患者预后的关系。方法:应用生物信息分析工具比对TCGA数据库中Snail基因mRNA在结直肠癌组织和癌旁组织中的表达水平;在STRING数据库中构建Snail蛋白-蛋白相互作用网络,并对相关蛋白功能和KEGG信号通路进行富集。同时,回顾性分析我院69例手术治疗的结直肠癌患者资料,根据Snail表达水平分为高、低表达组,比较两组患者总生存期(OS)和无疾病进展生存期(DFS)的差异。采用免疫组织化学法检测患者癌组织中Snail蛋白表达水平及其与患者临床病理特征的关系。结果:结直肠癌组织Snail基因mRNA表达水平明显高于癌旁组织;PDGFB基因与Snail呈正相关(r=0.624,P<0.05),SLC44A4基因与Snail呈负相关(r=–0.48,P<0.05)。Snail基因在生物学过程、细胞成分和分子功能方面分别富集于组蛋白H4脱乙酰化、ESC/E(Z)复合体和NAD依赖性组蛋白脱乙酰酶活性(H3-K14特异性)。KEGG信号通路富集于肿瘤相关信号通路、Notch信号通路、Wnt信号通路和结直肠癌相关信号通路等。生存分析显示,Snail高表达患者的OS低于低表达患者(HR=1.6,P<0.05),而Snail高、低表达患者的DFS差异无统计学意义(P>0.05)。Snail蛋白在结肠癌组织中的表达率为59.2%(41/69)。Snail蛋白高表达者在肿瘤分化程度、淋巴结转移、淋巴管侵犯率、Dukes分期等方面均差于低表达者,差异有统计学意义。结论:Snail基因在结直肠癌患者癌组织中表达水平上调,并可作为结直肠癌预后不良的分子标志物。

Objective To investigate the expression of snail in colorectal cancer,its signal pathway and its relationship with prognosis.Methods The expression level of snail gene mRNA in the TCGA database was compared with that in the colorectal cancer tissues and the adjacent tissues by using bioinformatics analysis tools.The interaction network of snail protein and protein was constructed in the string database and the function of related protein and KEGG signal pathway were enriched.According to the expression level of snail,the patients were divided into high and low expression groups.The differences of total survival(OS)and disease free progression survival(DFS)were compared.The relationship between the expression of snail protein and the clinicopathologicfeatures of 69 patients with colorectal cancer were analyzed by immunohistochemistry.Results The expression level of snail gene in colorectal cancer was significantly higher than that in the adjacent tissues.PDGFB gene(r=0.624,P<0.05)and slc44a4 gene(r=–0.48,P<0.05)were positively and negatively correlated with snail respectively.The biological process,cell composition and molecular function of snail are mainly enriched in histone H4 deacetylation,ESC/E(Z)complex and NAD dependent histone deacetylase activity(H3-K14 specificity)respectively.KEGG signal pathway was enriched in tumor related signaling pathway,Notch signaling pathway,Wnt signaling pathway and colorectal cancer related signaling pathway.The total survival rate of patients with high expression of snail gene mRNA was lower than that of patients with low expression(HR=1.6,P<0.05),while the survival rate of patients without disease progression in high and low expression group was statistically different(P>0.05).The high expression rate of snail protein in colorectal cancer was 59.2%(41/69).The high expression of snail protein in colorectal cancer had lower differentiation(P<0.05),higher lymph node metastasis(P<0.05),higher lymphatic invasion(P<0.05)and later Dukes stage(P<0.05).Conclusion The expression of snail gene is up-regulated in colorectal cancer and it can be used as a molecular marker of poor prognosis in colorectal cancer.