Longitudinal Analysis of Gene Expression Changes During Cervical Carcinogenesis Reveals Potential Therapeutic Targets.

Abstract

Despite advances in the treatment of cervical cancer (CC), the prognosis of patients with CC remains to be improved. This study aimed to explore candidate gene targets for CC. CC datasets were downloaded from the Gene Expression Omnibus database. Genes with similar expression trends in varying steps of CC development were clustered using Short Time-series Expression Miner (STEM) software. Gene functions were then analyzed using the Gene Ontology (GO) database and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Protein interactions among genes of interest were predicted, followed by drug-target genes and prognosis-associated genes. The expressions of the predicted genes were determined using real-time quantitative polymerase chain reaction (RT-qPCR) and Western blotting. Red and green profiles with upward and downward gene expressions, respectively, were screened using STEM software. Genes with increased expression were significantly enriched in DNA replication, cell-cycle-related biological processes, and the p53 signaling pathway. Based on the predicted results of the Drug-Gene Interaction database, 17 drug-gene interaction pairs, including 3 red profile genes (TOP2A, RRM2, and POLA1) and 16 drugs, were obtained. The Cancer Genome Atlas data analysis showed that high POLA1 expression was significantly correlated with prolonged survival, indicating that POLA1 is protective against CC. RT-qPCR and Western blotting showed that the expressions of TOP2A, RRM2, and POLA1 gradually increased in the multistep process of CC. TOP2A, RRM2, and POLA1 may be targets for the treatment of CC. However, many studies are needed to validate our findings.