结直肠癌肝转移新基因的生信筛选与免疫浸润分析

Bioinformatic screening and immunoinfiltration analysis for novel genes of colorectal cancer liver metastasis

[目的]基于生信技术筛选结直肠癌肝转移新基因,探究潜在治疗靶点。[方法]获取GEO数据库GSE221240、GSE41258和GSE6988三组数据集,筛选差异基因(DEGs),执行GO富集和KEGG通路分析,构建蛋白质互作网络(PPI)。利用GEPIA、HPA、TIMER 2.0进行差异表达分析、生存分析、免疫组化染色及免疫浸润分析,验证关键基因可靠度。[结果]获得30个DEGs,在肝转移样本中上调28个下调2个。GO富集和KEGG通路分析主要涉及急性期反应、脂质羟基化、DNA加合物致癌、细胞色素P450药物代谢等过程。PPI含有28个蛋白质节点与175条边。差异表达分析与生存分析验证得到2个结直肠癌肝转移新基因,即CYP2E1和ALDOB(P<0.05)。免疫组化染色结果证实,CYP2E1和ALDOB在结直肠、结直肠癌和肝脏组织中的蛋白表达存在明显差异。免疫浸润结果表明,CYP2E1和ALDOB的表达量与多种免疫细胞呈显著正相关(P<0.05)。[结论]通过生信筛选得到2个结直肠癌肝转移关键新基因CYP2E1和ALDOB。CYP2E1和ALDOB在肝组织的表达较结直肠组织显著上调,且与多种免疫细胞浸润显著相关,有望成为结直肠癌肝转移预后评估和治疗的新靶点。

[Objective] To screen new key genes and provide potential therapeutic target for colorectal cancer liver metastasis based on bioinformatics technology.[Method] Three datasets, GSE221240,GSE41258 and GSE6988,were obtained from the GEO database.Differential genes(DEGs) were screened for GO enrichment analysis and KEGG pathway analysis.Protein interaction network(PPI) was constructed.GEPIA,HPA,TIMER 2.0 databases were used for differential expression analysis, survival analysis, immunohistochemical staining level and immune infiltration analysis to verify the reliability of key genes. [Result] A total of 30 DEGs were obtained, with 28 up-regulated genes and 2 down-regulated genes in liver metastasis samples.GO enrichment and KEGG pathway analysis were mainly involved in acute phase reaction, lipid hydroxylation, DNA adduction chemical carcinogenesis, cytochrome P450 drug metabolism and other processes.PPI contained 28 protein nodes and 175 edges.Differential expression analysis and survival analysis verified two novel colorectal cancer liver metastasis genes named CYP2E1 and ALDOB(P<0.05).Immunohistochemical staining showed that CYP2E1 and ALDOB were significantly different in normal colorectal tissues, colorectal cancer tissues and liver tissues.The results of immunoinfiltration illustrated that the expression levels of CYP2E1 and ALDOB were significantly positively correlated with various immune cells(P<0.05).[Conclusion] Two new key genes of colorectal cancer liver metastasis, CYP2E1 and ALDOB,were identified by bioinformatic screening.The expression of CYP2E1 and ALDOB in liver tissues is significantly upregulated compared with that in colorectal tissues.Besides, the level of CYP2E1 and ALDOB expression is significantly correlated with a variety of immune cell infiltration.To sum up, CYP2E1 and ALDOB is expected to become new targets for prognosis evaluation and treatment of colorectal cancer liver metastasis.