Development and experimental verification of a prognosis model for cuproptosis-related subtypes in HCC

• Published in: Hepatology international Vol. 16; no. 6; pp. 1435 - 1447
• Main Authors: Wang, Yixiu, Zhang, Yongfa, Wang, Longrong, Zhang, Ning, Xu, Weiqi, Zhou, Jiamin, Zhao, Yiming, Zhu, Weiping, Zhang, Ti, Wang, Lu
• Format: Journal Article
• Language: English
• Published: New Delhi Springer India 01.12.2022; Springer Nature B.V
• Subjects: Algorithms; Apoptosis; Biomarkers, Tumor - genetics; Carcinoma, Hepatocellular - pathology; Cell activation; Cell death; Clusters; Colorectal Surgery; Copper; Data analysis; Destabilization; DNA methylation; Drug development; Gene expression; Gene Expression Regulation, Neoplastic; Genes; Hepatocellular carcinoma; Hepatology; Humans; Immunological memory; Iron-sulfur proteins; Liver cancer; Liver Neoplasms - pathology; Lymphocytes; Lymphocytes T; Medical prognosis; Medicine; Medicine & Public Health; Memory cells; Methylation; Microenvironments; Mitochondria; Mutation; Natural killer cells; Nomograms; Original Article; Patients; Prognosis; Proteins; Sensitivity analysis; Sulfur; Sulfur proteins; Surgery; Tumor Microenvironment - genetics; Tumors; Immune microenvironment; Molecular subtypes; Tumor metabolism; Tumor microenvironment; Cuproptosis; Nomogram; Hepatocellular carcinoma; Drug sensitivity analysis; Single-cell data analysis; Survival prognosis
• ISSN: 1936-0533; 1936-0541; 1936-0541
• DOI: 10.1007/s12072-022-10381-0

Background Cuproptosis is a recently discovered mechanism of programmed cell death caused by intracellular aggregation of mitochondrial lipoylated proteins and destabilization of iron-sulfur proteins triggered by copper. Hepatocellular carcinoma (HCC) is a common malignant tumor with a poor prognosis. We aimed to predict the survival of patients with HCC using the cuproptosis-related gene (CRG) expression. Methods We analyzed the expression, methylation, and mutation status of CRGs in 538 HCC patients and correlated the date with clinical prognosis. HCC patients were divided into two clusters based on their CRG expression. The relationship between CRGs, risk genes, and the immune microenvironment was analyzed using the CIBERSORT algorithm and the single-cell data analysis method. A cuproptosis risk model was constructed according to the five risk genes using the LASSO COX method. To facilitate the clinical applicability of the proposed risk model, we constructed a nomogram and conducted an antineoplastic drug sensitivity analysis. Results Our results suggest that the expression levels of CRGs in HCC are regulated by methylation. The prognoses were significantly different between the patients of the two clusters. The prognostic risk score positively correlated with memory T cell activation and negatively correlated with natural killer (NK) and regulatory T cell activation. Conclusion Our findings indicate the involvement of CRG regulation in HCC and provide new insights into prognosis assessment. Drug sensitivity analysis predicted drug candidates for the treatment of patients with different HCC subtypes. Graphical abstract