Integration of bulk and single-cell RNA-seq data identifies a cellular senescence-related prognostic signature in liver hepatocellular carcinoma

Liver hepatocellular carcinoma (LIHC) is a heterogeneous malignancy with poor prognosis, but the landscape of cellular senescence-related genes (CSRGs) in LIHC remains incompletely characterized. Here, we curated 167 CSRGs and performed integrative bulk and single-cell RNA-seq analyses using TCGA, ICGC, and TISCH datasets. Fifteen prognostic CSRGs were identified and stratified LIHC patients into two distinct molecular subtypes: Cluster 2 exhibited an immune-excluded phenotype with poor prognosis, whereas Cluster 1 represented an immune-desert phenotype. A CSRGs-based risk score was constructed and validated as an independent prognostic factor across cohorts. Single-cell analysis identified EEF1E1 as a key CSRG predominantly expressed in malignant hepatocytes, correlating with advanced clinicopathological features and immune infiltration. Functional experiments demonstrated that EEF1E1 knockdown significantly suppressed LIHC cell migration and invasion. Collectively, this study establishes a robust CSRGs-based prognostic signature. It also identifies EEF1E1 as a functionally relevant gene with oncogenic potential and a potential therapeutic target in LIHC.