A Bioinformatic Analysis Reveals Commonly Dysregulated Genes and Pathways in Multiple Cancers Treated with Metformin

Abstract Metformin, a prescribed medication for diabetes, has exhibited anti-cancer effects. In this study, we conducted an extensive bioinformatic analysis aiming to reveal effects of metformin on gene modulation in four distinct types of cancer: head and neck, liver, pancreatic, and prostate cancer. By integrating publicly available gene expression data from Gene Expression Omnibus (GEO) and enrichment analysis methods, we identified genes and pathways associated with the anti-cancer activities of metformin. We observed a significant upregulation of the genes NFKBIA and GADD45A, which are known to be involved in pathways linked to cancer progression. Moreover, we identified that MTHFD2 appears to be a biomarker for all these types of cancers and a target for metformin. Furthermore, the gene DKK1 exhibited potential as a prognostic indicator specifically for head and neck and pancreatic cancer, highlighting its clinical importance in these cancer types. In conclusion, our bioinformatic analysis suggests that metformin possesses anti-cancer activities through modulations of the NFKBIA, GADD45A, MTHFD2, and DKK1 genes which our study reveals for the first time their association with metformin in context of cancer. Our data contribute to understanding of the mechanism of anti-cancer activity of metformin.