Hepatitis B virus (HBV) infection is a significant cause of hepatocellular carcinoma (HCC). Dysregulated apoptosis causes tumor formation, progression, and treatment resistance in HBV-related HCC and is involved in its etiology. Nonetheless, the differentially expressed apoptosis-related genes (DEARGs) and underlying molecular mechanisms in HBV-related HCC remain unknown. In this study, two gene expression datasets (GSE47197 and GSE112271) of patients with HBV-related HCC were retrieved from public databases. A total of 86 DEARGs were identified via differential expression analysis. Subsequently, a series of bioinformatic analyses were performed on these DEARGs, such as enrichment analyses, random forest survival analysis, hub gene screening, immune infiltration analysis, specific signaling pathways analysis, nomogram model construction, prediction of miRNA and transcription factor (TF), and single cell analysis. Eventually, real-time quantitative polymerase chain reaction (RT-qPCR) was carried out to validate the hub gene expression analysis. A total of 86 DEARGs were identified in HBV-related HCC, among which two apoptosis-associated hub genes, namely DYNLL1 and FGFR2, were further characterized. Notably, these two genes are closely associated with tumor immune infiltration. In addition, GSVA and GSEA analyses further confirmed that the expression levels of DYNLL1 and FGFR2 directly regulated apoptosis-related signaling pathways, and the calibration curves and nomograms based on these two hub genes showed good performance in prognostic prediction for HBV-related HCC. Moreover, DYNLL1 and FGFR2 genes were found to be enriched in the transcription factor (TF) -binding sites of cisbpM6134, and single-cell analysis also clarified their expression patterns across various cell types. Finally, RT-qPCR validation results were consistent with our previous differential expression research. In summary, abnormal expression of DYNLL1 and FGFR2 genes in HBV-related HCC is linked to apoptosis and participates in multiple processes of tumor cell biology. DYNLL1 and FGFR2 genes may be promising predictive biomarkers for apoptosis and prognosis of HBV-related HCC.
Lei et al. (Mon,) studied this question.