Efferocytosis-related gene PLG in prognosis, immune correlation, and contribution to malignant behavior in vitro and in vivo of clear cell renal cell carcinoma

Efferocytosis plays an important role in tumor progression; however, its specific involvement in clear cell renal cell carcinoma (ccRCC) remains to be fully elucidated. In this study, efferocytosis-related genes (ERGs) were obtained from GeneCards and KEGG databases, and their expression profiles were analyzed in ccRCC using TCGA and GEO datasets. A total of 35 differentially expressed ERGs (DEGs) were identified. Among them, nine genes were found to be associated with overall survival using univariate Cox regression analysis. Consensus clustering further stratified patients into three molecular subtypes with distinct biological pathway characteristics. Subsequently, a risk score model based on six genes (PLAUR, MIAT, PLG, HAVCR1, ABCA1, and ABCG1) was constructed using LASSO regression and multivariate Cox analysis. This model stratified patients into high- and low-risk groups with significantly different survival outcomes. The risk score was significantly associated with overall survival and remained an independent factor in multivariate analysis. In addition, immune microenvironment analysis indicated that the risk score and model genes were closely related to immune characteristics. Among these genes, PLG was identified as a key gene with lower expression in tumor tissues. Functional experiments showed that PLG overexpression inhibited ccRCC cell proliferation and migration, reduced PD-L1 expression, and enhanced CD8⁺ T cell-mediated cytotoxicity. In summary, this study developed a risk score model associated with survival outcomes in ccRCC and highlighted a potential role of PLG in tumor progression and immune regulation. These findings provide a basis for further mechanistic studies and clinical validation.