Bioinformatic analysis of cervical cancer-associated hub genes and repurposing of 5-fluorouracil and gemcitabine as potential therapeutic agents

Abstract

Cervical cancer represents a major health issue worldwide. This study aimed to identify hub genes and signaling pathways associated with cervical cancer, and evaluate the efficacy of FDA-approved drugs against these hub proteins. From the Gene Expression Omnibus (GEO), we identified 239 genes (GSE26511) and 248 genes (GSE41827) that are differentially expressed in cervical cancer, which include 145 genes that are up-regulated and 94 that are down-regulated, along with 174 up-regulated genes and 74 down-regulated genes. By protein-protein interaction network (PPI) indicated 6 key genes for GSE26511 (ID2, FGF2, CLIC4, MED14, NGEF, TCF4) and 6 key genes for GSE41827 (ATF3, BCL2, MAF, MYC, TP53, HMOX). Molecular docking analysis of FDA-approved drugs (5-fluorouracil and gemcitabine) against 12 key proteins revealed potent binding affinities, with ID2 shown binding affinity of -5.2 kcal/mol when interacting with 5-fluorouracil, while CLIC4 shown a binding affinity of -7.2 kcal/mol with gemcitabine, along with 5 hydrogen bonds. Furthermore, MYC exhibit strong binding affinity with both drugs, and TP53 displayed a binding affinity of -5.6 kcal/mol with 5-fluorouracil and gemcitabine with hydrogen bonds. These results indicate that key proteins identified from the study show enhanced binding affinities with FDA-approved drugs, offering insights for targeted therapies in cervical cancer