Primary liver cancer poses a significant global health burden, with projections indicating a surpassing of one million cases by 2025. Cuproptosis, a copper-dependent mechanism of cell death, plays a crucial role in the pathogenesis, progression, and prognosis of various cancers, including hepatocellular carcinoma (HCC).

This study aimed to develop a prognostic model for HCC based on cuproptosis-related genes, utilizing clinical data and gene expression profiles from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases.

Clinical features and gene expression data of HCC patients were collected from publicly available databases. Patients from TCGA were randomly divided into training and testing sets, and Lasso Cox regression was applied to develop a predictive model using cuproptosis-related genes.

The analysis identified Copper Metabolism Domain Containing 1 (COMMD1) as a potential prognostic marker for HCC, with deletion of this gene impacting disease progression. Cellular functional experiments validated the role of COMMD1 in HCC.

COMMD1 emerges as a promising candidate for HCC treatment, with implications for prognosis prediction and therapeutic targeting.