Comprehensive Profiling and Therapeutic Insights into Differentially Expressed Genes in Hepatocellular Carcinoma

Simple Summary Hepatocellular carcinoma remains crucial due to its high prevalence and the need for improved understanding and treatment options. This study utilizes extensive microarray and RNA-seq data to identify key differentially expressed genes in hepatocellular carcinoma (HCC) and FDA-approved novel druggable genes. We uncovered potential associations between metal ion exposure and tumorigenesis, as well as the relevance of kinases in HCC. Topological analysis reveals 25 hub genes and their regulatory transcription factors, while computational drug repurposing suggests several novel therapeutic candidates targeting key genes, highlighting potential avenues for future experimental assays and clinical cohorts with HCC patients.Abstract Background: Drug repurposing is a strategy that complements the conventional approach of developing new drugs. Hepatocellular carcinoma (HCC) is a highly prevalent type of liver cancer, necessitating an in-depth understanding of the underlying molecular alterations for improved treatment. Methods: We searched for a vast array of microarray experiments in addition to RNA-seq data. Through rigorous filtering processes, we have identified highly representative differentially expressed genes (DEGs) between tumor and non-tumor liver tissues and identified a distinct class of possible new candidate drugs. Results: Functional enrichment analysis revealed distinct biological processes associated with metal ions, including zinc, cadmium, and copper, potentially implicating chronic metal ion exposure in tumorigenesis. Conversely, up-regulated genes are associated with mitotic events and kinase activities, aligning with the relevance of kinases in HCC. To unravel the regulatory networks governing these DEGs, we employed topological analysis methods, identifying 25 hub genes and their regulatory transcription factors. In the pursuit of potential therapeutic options, we explored drug repurposing strategies based on computational approaches, analyzing their potential to reverse the expression patterns of key genes, including AURKA, CCNB1, CDK1, RRM2, and TOP2A. Potential therapeutic chemicals are alvocidib, AT-7519, kenpaullone, PHA-793887, JNJ-7706621, danusertibe, doxorubicin and analogues, mitoxantrone, podofilox, teniposide, and amonafide. Conclusion: This multi-omic study offers a comprehensive view of DEGs in HCC, shedding light on potential therapeutic targets and drug repurposing opportunities.

Automated summary

This study provides a comprehensive analysis of differentially expressed genes in hepatocellular carcinoma (HCC), identifying potential therapeutic targets and opportunities for drug repurposing.