The efferocytosis-related genes of SLC26A6, TYRO3, and PDK4 have been identified as predictors of prognosis in hepatocellular carcinoma and are associated with the immune status

Background: Efferocytosis plays a critical role in clearing apoptotic tumor cells and suppressing inflammation in hepatocellular carcinoma (HCC).This study aimed to identify efferocytosis-related genes (ERGs) with prognostic value and develop a predictive model for HCC outcomes.Methods: Using public HCC transcriptomic and clinical data, we identified 13 differentially expressed ERGs (DE-ERGs) from 3,866 DEGs and 74 known ERGs.Cox regression analysis selected SLC26A6, TYRO3, and PDK4 as key prognostic genes for risk model construction.The model, combined with pathologic T stage in a nomogram, showed high predictive accuracy for patient survival.Results: Totally 13 DE-ERGs were gained by overlapping 3,866 DEGs and 74 ERGs, and SLC26A6, TYRO3, and PDK4 were identified as prognosis genes for constructing a risk model with highly proficient in assessing the risk of HCC patients.Then, both risk score and pathologic T stage were recognized as independent factors prognosticating the outcome of HCC patients.Afterwards, we constructed a nomogram utilizing risk score and pathologic T stage to achieve high accuracy in predicting the survival outcomes of HCC patients.Groups at low risk demonstrated enrichment in pathways related to biometabolism and immune response, such as "fatty acid metabolism" and "complement and coagulation cascades".Additionally, the strongest positive and negative correlation were observed from activated CD4 + T cell and TYRO3 (cor = 0.37), as well as natural killer cell and SLC26A6 (cor = -0.35),respectively.And risk score exhibited strong predictive capacity in response to immunotherapy.Moreover, lncRNA-miRNA-mRNA network included complex interaction pairs, such as TYRO3-hsa-miR-203b-5p-NUTM2A-AS1.There were 61 drugs with significant differences in IC50 between the high and low risk groups, such as BI.2536 and PD-173074.Single-cell analysis identified hepatocytes as the key cell population, exhibiting dynamic prognostic gene expression during differentiation and disease-specific alterations in cell-cell communication through ligand-receptor interactions.Conclusion: We identified three prognostic genes associated with efferocytosis in HCC and integrated them into a risk prognostic model.These genes not only serve as signatures for predicting HCC prognosis but also offer insights into the treatment of HCC.