An Immunogenic Cell Death-Related Genes Predicts Prognosis And Tumor Microenvironment Features Of Early-stage Primary Hepatic Cell Carcinoma Patients

Abstract

Abstract Objective To elucidate the potential relationship between ICD and early-stage HCC prognosis, we sought to identify ICD-related genes and construct a model predicting patient response and survival outcomes to immunotherapy. Methods A cohort of 252 early-stage HCC patients was obtained from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx). Immunogenic Cell Death-associated Gene Signatures (ICD-AGS) were curated from 57 genes implicated in ICD. Comparative analysis identified differentially expressed ICD-associated genes (DE-IRGs), which were subsequently functionally annotated using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway mapping.The relationship between ICD expression and the immune microenvironment was assessed using the ESTIMATE and CIBERSORT algorithms. A risk model was constructed through univariate Cox regression, LASSO technique, and gene expression profiling, validated with ROC curve analysis. Results Consensus clustering identified two distinct ICD expression groups, with the high-expression group associated with a favorable prognosis. Differential gene expression analysis revealed enrichment in immune-related pathways in the high ICD expression group. Somatic mutation analysis indicated variations in TP53, CTNNB1, and MUC16 between the two groups. The ICD high-expression group exhibited increased immune cell infiltration and higher expression of immune checkpoints. The ICD risk model containing 8 genes showed significant prognostic value and was externally validated. Conclusion This study unveils a novel relationship between ICD subtypes and the immune tumor microenvironment in early-stage HCC. The established prognostic risk model related to ICD provides valuable insights for predicting patient outcomes and guiding immunotherapeutic interventions in HCC.