Identification of microRNA Signature and Key Genes Between Adenoma and Adenocarcinomas Using Bioinformatics Analysis

In worldwide, colorectal cancer (CRC) is very common and the mechanisms remain unclear. This study aims to identify between adenomas with epithelial dislocation (false invasion) and adenomas with early adenocarcinoma (true invasion).

GSE41655 and GSE57965 datasets were obtained in the Gene Expression Omnibus (GEO) database. microRNA expression profiles and clinicopathological data from the TCGA (The Cancer Genome Atlas) database were downloaded to further validate the results in GEO. GEO software and the GEO2R calculation method were used to analyze two gene profiles. The co-expression of differentially expressed microRNAs (DEMs) and genes (DEGs) were identified and searched in the FunRich databases for pathway and ontology analysis. Cytoscape was utilized to construct the mRNA-microRNA network. Validation of gene expression levels was conducted by online databases and qRT-PCR and IHC experiments.

In total, 6 DEMs and 34 DEGs are selected after calculating. KEGG results indicated that genes are enriched in certain tumor associated pathways. Four out of 6 microRNAs had a significant relationship with the overall survival (P < 0.05) and showed a good performance in predicting the survival risk of patients with colorectal carcinoma. Furthermore, expression levels of hsa-miR-455 and hsa-miR-125a were then verified by qRT-PCR which all target BCL2L12. IHC results showed that the expression level of BCL2L12 was higher in adenocarcinoma than in adenoma. Based on the selected gene, the top 10 small molecules were screened out as potential drugs.

By using microarray and bioinformatics analyses, DEMs and DEGs were selected and a complete gene network was constructed. To our knowledge, BCL2L12 and related molecules including hsa-miR-455 and hsa-miR-125a were firstly identified as potential biomarkers in the progression from adenoma to adenocarcinoma.