Abstract / Summary
Abstract Background: Colorectal cancer (CRC) remains a major global health challenge, characterized by uncontrolled abnormal cell growth of colon and rectal epithelial cells. Recent clinical trials suggest that probiotic strategies can suppress CRC progression, but the convergent mechanism through which these probiotics act remains unknown. Hypothesis: This study hypothesized that, despite differences in probiotic strains and mechanisms of action, probiotics could converge on a shared set of regulatory hub genes and signaling pathways to exert coloprotective effects. Methods: We employed an integrative bioinformatics approach that combined two independent GEO datasets, GSE115081 and GSE67033, involving two different probiotic strains. We further identified overlapping differentially expressed genes (DEGs) between the two probiotic treatments. Finally, protein-protein interaction network analysis was performed using the STRING database, along with Gene Ontology, KEGG, and Reactome pathway enrichment analyses, to functionally characterize the architecture of this shared gene set. Results: Overlapping DEGs from GEO datasets revealed 422 shared genes present across both datasets. Furthermore, enrichment analyses converged on three interconnected pathways viz. inflammatory signaling (centered on TNF/NF-κB), the integrated stress response and proteostasis (unfolded protein response), and cell death signaling. We also performed hub gene analysis, which identified MYC, TNF, HSP90AA1, NFKBIA, IL1B, FOS, and ATF3 as central nodes within this network. Conclusion: T hese findings identify the converging mechanism of action of probiotics and identify hub genes and pathways as candidate biomarkers and targets for future mechanistic and translational studies.