Integrative Genomic Analysis Reveals Pseudouridine Modification-Related Gene Signatures Associated With Prognosis and Therapeutic Response Patterns in Hepatocellular Carcinoma

<h4>Background</h4>Hepatocellular carcinoma (HCC) is a genomically heterogeneous malignancy with substantial variability in prognosis and therapeutic response. Pseudouridine (<i>Ψ</i>) modification is an evolutionarily conserved RNA modification involved in RNA structure stabilization and translational regulation; however, the genomic and functional relevance of pseudouridine modification-related genes (PDGs) in HCC remains poorly defined.<h4>Methods</h4>Transcriptomic datasets and matched clinical information were collected from TCGA, GEO, and ICGC. Using feature-selection procedures and survival modeling, we established a pseudouridine-related risk signature. We next compared risk groups for genomic change, pathways, immune traits, and predicted drug response. Selected genes were tested in HCC cells by qPCR and CCK-8.<h4>Results</h4>The PDGs signature split HCC patients into high- and low-risk groups with different survival and remained prognostic after adjustment. The groups also differed in mutation, pathways, immunity, and chemotherapy response. DKC1 and PUS1 knockdown reduced proliferation.<h4>Conclusions</h4>This study identifies a PDGs signature linked with prognostic heterogeneity in HCC, supported by computational and experimental evidence.