Abstract
Background
Copper homeostasis imbalance has been implicated in tumor progression, aggressiveness, and treatment response. However, the precise roles of cuproptosis-related genes (CRGs) in hepatocellular carcinoma (HCC) remain poorly understood.
Methods
In this study, we employed a consensus clustering algorithm to identify distinct molecular subtypes. We then performed Kaplan–Meier analysis and univariate Cox regression analysis to identify prognostic differentially expressed genes. The expression of these genes was subsequently validated using qPCR on fresh-frozen tissues obtained from HCC patients. Moreover, leveraging the TCGA-HCC cohort, we constructed a CRGs-related risk prediction model using the LASSO and multivariate Cox regression analysis.
Results
By analyzing the data, we successfully established a CRGs risk prognostic model for HCC patients, comprising five differential genes (CAD, SGCB, TXNRD1, KDR, and MTND4P20). Cox regression analysis revealed that the CRGs risk score could serve as an independent prognostic factor for overall survival (hazard ratio [HR] = 1.308, 95% confidence interval [CI] = 1.200 − 1.426, P < 0.001). The area under the curve (AUC) values of the CRGs-score for predicting 1-year, 3-year, and 5-year survival rates were 0.785, 0.724, and 0.723, respectively. Notably, the expression levels of immune checkpoints (including PD-1, PD-L1, and CTLA4) significantly differed between the low- and high-risk score groups. Furthermore, the low-risk score group displayed increased sensitivity to sorafenib, cisplatin, cyclopamine, nilotinib, salubrinal, and gemcitabine, whereas the high-risk score group exhibited heightened sensitivity to lapatinib, erlotinib, and gefitinib.
Conclusions
Our findings highlight the potential of the CRGs risk score as an independent and promising biomarker for clinical prognosis and immunotherapy sensitivity in HCC patients.
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Availability of data and materials
The raw data used in this article were retrieved from public databases (https://portal.gdc.cancer.gov/repository). All analyzed data are included in this published article and its supplementary information file, which are available from the corresponding author upon reasonable request.
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Funding
This work was supported by the National Natural Science Foundation of China (81772276) and Hubei Provincial Natural Science Fund for Creative Research Groups (2019CFA018).
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SX, WC, and S-ML conceived and drafted the original manuscript; SX and YY conducted data analysis and bioinformatics analysis; KD, and RG performed the experiments. S-ML, YZ, and CL revised the manuscript for intellectual content. S-ML conduced project administration. All authors reviewed and approved the final version prior to its submission.
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The processing of clinical tissue samples is in strict compliance with the ethical standards of the Declaration of Helsinki. The present study was approved by the ethics committee of Zhongnan Hospital of Wuhan University (Approval number: 2017058). Written informed consent was obtained from all the participants.
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Xu, S., Dong, K., Gao, R. et al. Cuproptosis-related signature for clinical prognosis and immunotherapy sensitivity in hepatocellular carcinoma. J Cancer Res Clin Oncol 149, 12249–12263 (2023). https://doi.org/10.1007/s00432-023-05099-x
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DOI: https://doi.org/10.1007/s00432-023-05099-x