Abstract:

This study aimed to investigate the effect of copper-induced cell death-related genes on hepatocellular carcinoma (HCC) and to explore active components for treating HCC. The GSE84402 dataset was downloaded from the Gene Expression Omnibus (GEO) database to obtain the differentially expressed genes associated with HCC, and copper-induced cell death-related genes were retrieved from past literature; the commonalities between the two were considered to obtain HCC-related copper-induced cell death genes. The genes in common were further analyzed for differential expression using the UALCAN (University of Alabama at Birmingham Cancer Data Analysis) portal, the correlation between their expression levels and clinical levels was analyzed using the R language, prognostic value was determined using the Kaplan-Meier plotter, their relationship with HCC metastasis was examined using the Human Cancer Metastasis Database (HCMDB), and their pathological relationship with HCC was explored using the Treponema pallidum hemagglutination test. Lastly, compound prediction and molecular docking were performed. The results showed that compared with the normal group, expression levels of the key copper-induced cell death genes SLC31A1 and DBT were downregulated in tumors, and pathological analysis showed that their proteins were increased in HCC tissues. In addition, these genes were significantly correlated with the clinical correlation variables of sex, tumor stage, and lymph node metastasis. Their high expression was correlated with a good HCC prognosis, whereas low expression of SLC31A1 was significantly correlated with the metastasis of HCC to the adrenal glands and lungs. Finally, the active compounds that may bind to SLC31A1 and DBT were screened, of which resveratrol and folic acid exhibited high docking scores. Hence, it could be concluded that copper-induced cell death-related genes SLC31A1 and DBT play an important role in the development of HCC, and this study provides new theories for the diagnosis of HCC and therapeutic drug research.

Key words: hepatocellular carcinoma, cuproptosis, SLC31A1, DBT