基于mRNA和miRNA芯片探索影响结直肠癌肝转移的靶基因

Screening potential targets for liver metastasis of colorectal cancer using combined miRNA and mRNA microarray analysis

目的筛选与结直肠癌(CRC)肝转移相关的靶基因。方法从Gene Expressed Omnibus(GEO)数据库下载mRNA和miRNA的表达谱(GSE30687和GSE44121)。通过limma函数包分析得出差异表达mRNA和差异表达miRNA。基于DAVID在线工具进行差异表达mRNA的GO功能富集分析和KEGG通路富集分析。利用TargetScan筛选由差异表达miRNA调节的靶基因,并构建miRNA-mRNA调节网络。结果与原发性CRC样品相比,在具有肝转移的CRC样品中筛选出180个差异表达mRNAs,其中116个表达下调,64个表达上调,另外筛选出15个差异表达miRNAs,表达上调的有6个,表达下调的有9个。差异表达mRNAs富集于32个GO terms中,如阴离子运输、细胞的顶端部分、脱氧核糖核酸酶活性等。另外,这些差异表达mRNAs主要富集在包括类固醇生物合成和霍乱弧菌感染在内的2条通路中。miRNA-mRNA调控网络包括50个miRNA-mRNA关系对,其中具有较高节点度的基因为纤连蛋白1(FN1)和骨髓嗜病毒整合位点1(MEIS1)。结论FN1 和MEIS1 基因可能是大肠癌肝转移的潜在生物标志物。

Objective To screen target genes related to liver metastasis in colorectal cancer (CRC). Methods The mRNA and miRNA expression profiles (GSE30687 and GSE44121) were downloaded from the Gene Expressed Omnibus (GEO) database. The differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) were identified through the limma software package, respectively. The database for Annotation, Visualization and Integrated Discovery (DAVID) was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of DEGs. Targets regulated by DEMs were screened by TargetScan, and the miRNA-mRNA regulated network was constructed. Results Compared with non-metastatic CRC samples, there were 180 mRNAs and 15 miRNAs in DEMs in CRC samples with liver metastasis, respectively. DEGs were enriched in 32 GO terms and 2 KEGG pathways. In 50 miRNA-mRNA pairs involved in the miRNA-mRNA network, there were genes with higher node degrees including FN1 and MEIS1. Conclusion FN1 and MEIS1 genes might be potential biomarkers of CRC with liver metastasis.