A novel ubiquitination-related gene signature for overall survival prediction in patients with liver hepatocellular carcinoma

Discov Oncol. 2025 Jan 21;16(1):71. doi: 10.1007/s12672-025-01768-0.

Abstract

Liver hepatocellular carcinoma (LIHC) is a highly heterogeneous disease, necessitating the discovery of novel biomarkers to enhance individualized treatment approaches. Recent research has shown the significant involvement of ubiquitin-related genes (UbRGs) in the progression of LIHC. However, the prognostic value of UbRGs in LIHC has not been investigated. In this study, the mRNA expression profiles and clinical data were obtained from public databases of LIHC patients. The least absolute shrinkage and selection operator Cox regression model was employed to construct a multigene signature in the TCGA cohort. Our results showed that a twelve UbRGs signature was developed to categorize patients into two risk groups, with significant differences in expression between LIHC and normal tissues. Patients in the high-risk group exhibited significantly reduced overall survival (OS) and progression-free survival compared to those in the low-risk group. The risk score was identified as an independent predictor for OS in multivariate Cox regression analyses. Receiver operating characteristic curve analysis confirmed the predictive capacity of the signature. Functional analysis revealed enrichment of immune-related pathways and differences in immune status between the two risk groups. The risk score was correlated with 35 transcription factors and 26 eRNA enhancers, and positively associated with tumor mutation burden. Patients in the high-risk group demonstrated decreased sensitivity to targeted and chemotherapeutic drugs than those in the low-risk group. In conclusion, our study identified a twelve UbRGs signature that may serve as a prognostic predictor for LIHC patients and and provide valuable insights for cancer treatment.

Keywords: Functional analysis; Liver hepatocellular carcinoma; Overall survival; Ubiquitin; Ubiquitin-related gene pair.