A Systems Biology Approach to Identify Novel Biomarkers in Progression from Crohn’s Disease to Colorectal Cancer

OBJECTIVE: This study aimed to find the key genes and miRNAs as potential biomarkers related to the progression of colorectal cancer (CRC) from Crohn’s disease (CD). BACKGROUND: CD is widely accepted as one of the main risk factors leading to CRC. So, Identifying the novel molecular pathways involved in the development of CRC from CD can provide potential solutions for therapeutic interventions. METHODS: By implementing a systematic approach, we have analyzed mRNA and miRNA datasets containing CRC and CD samples to determine differentially expressed genes (DEGs) and miRNAs (DEmiRNA). Then by selecting common genes involved in the progression from CD to CRC, different downstream analyses including mRNA-miRNA network, functional enrichment analysis, gene set enrichment analysis, and survival analysis were performed. Finally, quantitative real-time PCR (RT-PCR) analysis of tissue samples obtained from Normal/CRC samples was used to confirm the differential expression of selected genes and miRNA. RESULTS: There were 10 DE miRNA and 181 genes DEGs common between progression from CD to CRC. The genes obtained for each of the 10 miRNAs were considered as the final target for downstream analyzes. In addition, analysis of RT-PCR indicated that miR-195-5p, PHLPP2, and LITAF were downregulated in the cancer group compared to the control group. CONCLUSION: This study showed that PHLPP2, LITAF, and miR-195-5p may have key roles in the tumorigenesis of CRC and they can be used as therapeutic targets and diagnostic biomarkers after further in-vitro and in-vivo evaluation.