Identification of Five Hub Genes as Key Prognostic Biomarkers in Liver Cancer via Integrated Bioinformatics Analysis

SIMPLE SUMMARY: Liver cancer is one of the most common cancers; however, the molecular mechanisms of liver tumorigenesis and progression are not completely understood. In the current study, we combined several bioinformatic approaches (differential gene expression analyses, weighted gene co-expression network analysis, pathway and gene-disease network enrichment) to identify potential hub genes and molecular pathways that contribute to liver cancer onset and development. The results revealed DNA topoisomerase II alpha (TOP2A), ribonucleotide reductase regulatory subunit M2 (RRM2), never in mitosis-related kinase 2 (NEK2), cyclin-dependent kinase 1 (CDK1), and cyclin B1 (CCNB1) as the hub genes for liver cancer. Subsequent validation suggested TOP2A, RRM2, NEK2, CDK1, and CCNB1 as the prognostic biomarkers of liver cancer. ABSTRACT: Liver cancer is one of the most common cancers and the top leading cause of cancer death globally. However, the molecular mechanisms of liver tumorigenesis and progression remain unclear. In the current study, we investigated the hub genes and the potential molecular pathways through which these genes contribute to liver cancer onset and development. The weighted gene co-expression network analysis (WCGNA) was performed on the main data attained from the GEO (Gene Expression Omnibus) database. The Cancer Genome Atlas (TCGA) dataset was used to evaluate the association between prognosis and these hub genes. The expression of genes from the black module was found to be significantly related to liver cancer. Based on the results of protein–protein interaction, gene co-expression network, and survival analyses, DNA topoisomerase II alpha (TOP2A), ribonucleotide reductase regulatory subunit M2 (RRM2), never in mitosis-related kinase 2 (NEK2), cyclin-dependent kinase 1 (CDK1), and cyclin B1 (CCNB1) were identified as the hub genes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses showed that the differentially expressed genes (DEGs) were enriched in the immune-associated pathways. These hub genes were further screened and validated using statistical and functional analyses. Additionally, the TOP2A, RRM2, NEK2, CDK1, and CCNB1 proteins were overexpressed in tumor liver tissues as compared to normal liver tissues according to the Human Protein Atlas database and previous studies. Our results suggest the potential use of TOP2A, RRM2, NEK2, CDK1, and CCNB1 as prognostic biomarkers in liver cancer.