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Integrative Genomic Analysis Reveals Pseudouridine Modification-Related Gene Signatures Associated With Prognosis and
Zeying Gan1, Tingyuan Fan2, Wenjuan Wang3
1Department of Critical Care Medicine, The Fourth Hospital of Changsha (Integrated Traditional Chinese and Western Medicine Hospital of Changsha, Changsha Hospital of Hunan Normal University), Changsha, China.
Background:
Hepatocellular carcinoma (HCC) is a genomically heterogeneous malignancy with substantial variability in prognosis and therapeutic response. Pseudouridine (Ψ) 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.
Methods:
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.
Results:
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.
Conclusions:
This study identifies a PDGs signature linked with prognostic heterogeneity in HCC, supported by computational and experimental evidence.
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