基于全基因组表达谱芯片数据集对结肠癌肝转移可能机制的初步研究

A preliminary study on the potential mechanisms of colon cancer liver metastasis using genome-wide expression microarray dataset

目的通过GEO数据库中结肠癌肝转移的全基因组表达谱芯片数据集进行基因集富集分析(GSEA),探索结肠癌肝转移的相关机制。方法从GEO数据库中下载结肠癌肝转移的相关数据集GSE92914,以结肠癌肝转移患者的结肠原发癌组织、结肠癌旁正常组织和肝转移灶组织作为分组变量,以“c5.all.v7.0.symbols.gmt”作为参照基因集,使用GSEA-4.0.2版本进行分析。结果结肠原发癌的发生可能与激素代谢过程、T细胞增殖的正调控、NF-κB转录因子活性的正调控等生物学功能有关。对比肝转移灶组织和结肠癌旁正常组织,发现在肝转移灶组织中可以显著富集到泛素依赖蛋白分解代谢过程的正调控、去磷酸化调节和磷酸酶活性的调节等生物学功能表现。对比结肠原发癌组织和肝转移灶组织,发现在肝转移灶组织中可以显著富集到淋巴细胞分化、白细胞分化和电子传递活性等生物学功能表现。结论结肠癌肝转移灶的产生机制相较于结肠癌原发灶可能出现了改变,淋巴细胞分化、白细胞分化和电子传递活性等生物学功能可能参与了结肠癌肝转移的发生。

Objectives Gene set enrichment analysis(GSEA)was performed to investigate the potential mechanisms of colon cancer liver metastasis by analyzing the genome-wide expression microarray dataset in the Gene Expression Omnibus(GEO)data?base.Methods The dataset GSE92914 related to colon cancer liver metastasis was downloaded from the GEO database.With‘c5.all.v7.0.symbols.gmt’as the reference gene set,GSEA(version 4.0.2)was conducted on primary colon cancer,adjacent nor?mal tissue,and liver metastasis tissue of patients with colon cancer.Results The mechanism of primary colon cancer may be re?lated to hormone metabolism,positive regulation of T cell proliferation,and positive regulation of NF-κB transcription factor activ?ity.Compared with adjacent normal tissue,it was found that liver metastasis tissue can be significantly enriched in biological functions such as positive regulation of ubiquitin-dependent protein catabolism,regulation of dephosphorylation,and regulation of phosphatase activity.Compared with primary cancer tissue,significant enrichment of lymphocyte differentiation,leukocyte differenti?ation,and electron transfer activity was found in liver metastasis tissue.Conclusion Compared with primary colon cancer,the mechanism of liver metastasis might be altered and be associated with lymphocyte differentiation,leukocyte differentiation,and electron transfer activity.