Construction of an immune-related prognostic model and functional analysis of CEBPB in uveal melanoma: A STROBE-compliant observational study

Uveal melanoma (UM) is a primary intraocular malignancy with a high-risk of metastasis. Currently, there are no studies that construct prognostic models based on immune-related molecular subtypes. We performed unsupervised clustering of immune cell infiltration matrices based on the the cancer genome atlas-uveal melanoma (TCGA-UVM) dataset, identifying 2 clusters with distinct expression patterns of immune checkpoint and immune activation related genes. gene ontology/Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that genes in the immune-related gene modules identified by WGCNA were associated with immune activity and cell proliferation. Using Cox and LASSO regression analysis based on the immune-related gene modules to construct a prognostic model. The prognostic model was validated in external datasets of Gene Expression Omnibus (GEO) database. We constructed a prognostic model comprising genes S100A4, KCNIP3, PARP8, ORAI2, MMP12, ISG20, MMP9, and CEBPB. The model stratified patients into high and low-risk groups, with the high-risk group showing poorer prognosis. The model's predictive accuracy was validated with the AUC values exceeding 0.8 for 1-year, 3-year, and 5-year survival rates and confirmed in external datasets GSE22138 and GSE84976. Differential gene analysis between risk groups highlighted the association with immune response and cell proliferation functions. The CEBPB gene in the model played crucial roles in tumor progression. In vivo and in vitro experiments validated the impact of CEBPB on the biological functions of UM. Experiments in UM cells revealed that CEBPB promoted cell proliferation, migration and invasion, as well as suppressing apoptosis, indicating its potential as a therapeutic target. The prognostic model based on 8 immune-related genes effectively predicted the survival outcomes of UM. Knockdown of CEBPB significantly reduced the progression of UM, suggesting that it could be a potential therapeutic target for UM.