Introduction: Hepatocellular Carcinoma (HCC) is a malignant tumor originating from liver cells, with extremely high incidence and mortality rates. Cell necrotic apoptosis and immune dysregulation play significant roles in HCC. Methods: This study aims to investigate the prognosis and expression regulation mechanisms of necrotic apoptosis genes and their immune modulatory genes in HCC. The data sets of HCC were collected from The Cancer Genome Atlas (TCGA). One thousand four hundred fifteen Differentially Expressed Genes (DEGs) between normal tissues and tumor tissues in HCC were screened. PLK1 was selected as a target gene for the study between DEGs and necrotic-apoptosis gene sets. It is significantly associated with the prognosis of HCC. Results: Our findings showed that the PLK1 gene was overexpressed in HCC, and that immune cell infiltration and the Tumor Microenvironment (TME) were closely related to PLK1 expression levels in HCC, with obvious differences in PLK1 immunohistochemistry between normal and HCC tissues. According to PLK1-related immunomodulators, a three-gene (KDR, CD27, and TNFRSF4) prognostic model was established. Survival analysis demonstrated that the Overall Survival (OS) of high-risk patients was significantly worse than that of low-risk patients with HCC. The reliability and predictive power of the risk-score model were assessed using a receiver operating characteristic curve. And the independent external dataset was used to validate these results. Discussion: These results suggest that PLK1 is not only a key prognostic biomarker in HCC but also a central regulator linking necroptosis and immune dysregulation within the tumor microenvironment. The established three-gene prognostic model underscores the potential of immune modulators as predictive tools for patient stratification. Conclusion: The findings of this study provided a reference for understanding the pathogenesis of HCC. The identified genes and their relationships may serve as potential targets for further research on the diagnosis, treatment, and prognosis of HCC.
Wang et al. (Mon,) studied this question.