Uncovering New Biomarkers in the Transition from Crohn’s Disease to Colorectal Cancer: A Systems Biology Perspective
Uncovering New Biomarkers in the Transition from Crohn’s Disease to Colorectal Cancer: A Systems Biology Perspective
Niloofar Shokrollah,1Saeid Afshar,2,*
1. Al-Zahra Educational and Remedial Center, Guilan University of Medical Sciences, Rasht, Iran 2. Cancer Research Center, Hamadan University of Medical Sciences, Hamadan, Iran
Introduction: Colorectal cancer (CRC) is one of the most prevalent malignancies worldwide, and its development is often linked to chronic inflammatory conditions of the gastrointestinal tract, particularly Crohn’s disease (CD). CD, a type of inflammatory bowel disease (IBD), is widely recognized as a significant risk factor for CRC, as prolonged inflammation can lead to cellular damage, genetic mutations, and eventually tumorigenesis. Despite this established connection, the molecular mechanisms driving the progression from CD to CRC remain inadequately understood.
Identifying key genetic and molecular factors involved in this transition could lead to novel therapeutic targets and improved diagnostic tools. In particular, the role of differentially expressed genes (DEGs) and microRNAs (miRNAs), which regulate gene expression post-transcriptionally, is of growing interest. miRNAs can act as oncogenes or tumor suppressors, influencing cancer progression through the regulation of key cellular pathways. Therefore, this study aimed to uncover crucial DEGs and miRNAs associated with CRC progression from CD, with the goal of identifying potential biomarkers and therapeutic targets.
Methods: We employed a systematic approach to analyze mRNA and miRNA datasets comprising samples from both CRC and CD patients to identify differentially expressed genes (DEGs) and miRNAs (DEmiRNAs). Common genes associated with the progression from CD to CRC were selected for further analysis, including mRNA-miRNA interaction network construction, functional enrichment analysis, gene set enrichment analysis, and survival analysis. To validate the findings, quantitative real-time PCR (RT-PCR) was performed on tissue samples from normal and CRC patients to confirm the differential expression of selected genes and miRNAs.
Results: We identified 10 differentially expressed miRNAs and 181 differentially expressed genes common to the progression from CD to CRC. The genes associated with each of these 10 miRNAs were used for downstream analyses. RT-PCR results confirmed that miR-195-5p, PHLPP2, and LITAF were significantly downregulated in CRC tissues compared to controls.
Conclusion: Our findings suggest that PHLPP2, LITAF, and miR-195-5p may play crucial roles in CRC tumorigenesis and could be considered potential therapeutic targets and diagnostic biomarkers, pending further in vitro and in vivo validation.
Keywords: Colorectal cancer (CRC),Crohn’s disease (CD),Biomarkers,miRNAs,Differentially expressed genes (DEGs)