Finding key genes (UBE2T, KIF4A, CDCA3, and CDCA5) co-expressed in hepatitis, cirrhosis and hepatocellular carcinoma based on multiple bioinformatics techniques

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Hepatitis B virus (HBV) is one of the major causes of liver cirrhosis (LC) and HCC. Therefore, the discovery of common markers for hepatitis B or LC and HCC is crucial for the prevention of HCC.

Expressed genes for to chronic active hepaititis B (CAH-B), LC and HCC were obtained from the GEO and TCGA databases, and co-expressed genes were screened using Protein-protein interaction (PPI) networks, least absolute shrinkage and selection operator (LASSO), random forest (RF) and support vector machine - recursive feature elimination (SVM-RFE). The prognostic value of genes was assessed using Kaplan-Meier (KM) survival curves. Columnar line plots, calibration curves and receiver operating characteristic (ROC) curves of individual genes were used for evaluation. Validation was performed using GEO datasets. The association of these key genes with HCC clinical features was explored using the UALCAN database (https://ualcan.path.uab.edu/index.html).

Based on WGCNA analysis and TCGA database, the co-expressed genes (565) were screened. Moreover, the five algorithms of MCODE (ClusteringCoefficient, MCC, Degree, MNC, and DMNC) was used to select one of the most important and most closely linked clusters (the top 50 genes ranked). Using, LASSO regression model, RF model and SVM-RFE model, four key genes (UBE2T, KIF4A, CDCA3, and CDCA5) were identified for subsequent research analysis. These 4 genes were highly expressed and associated with poor prognosis and clinical features in HCC patients.

These four key genes (UBE2T, KIF4A, CDCA3, and CDCA5) may be common biomarkers for CAH-B and HCC or LC and HCC, promising to advance our understanding of the molecular basis of CAH-B/LC/HCC progression.