Establishment and validation of a cuproptosis-related lncRNA signature that predicts prognosis and potential targeted therapy in hepatocellular carcinoma

ABSTRACT

Background: Cuproptosis is a recently identified form of programmed cell death and could be a new direction for tumour therapy, and it has important clinical implications. Long non-coding RNAs (lncRNAs) can intervene in diverse biological processes and have a decisive role in hepatocellular carcinoma (HCC). However, how cuproptosis-related lncRNAs (CRLs) participate in regulating HCC has yet to be recognised. This study aimed to establish and validate a prognostic signature of CRLs and to analyse their clinical value in HCC patients. Methods: To analyse the function of CRLs in the prognosis of HCC, RNA sequencing data, mutation data, and clinically relevant data were collected from the Cancer Genome Atlas Database (TCGA). Then, TCGA cohort was randomly divided into training and test sets. The training set was utilized to define prognostic signature of CRLs using bioinformatics methods. Subsequently, we verified the accuracy of this prognostic signature in the test set. Finally, we performed immune-related analysis, the half-maximal inhibitory concentration (IC50) prediction, gene set enrichment analysis, and tumour mutational burden (TMB) analysis. Results: We established a prognostic signature for the CRLs (SNHG4, AC026412.3, AL590705.3, and CDKN2A-DT). This signature-based risk group displayed an accurate predictive ability for the survival time of patients with HCC. We observed discrepancies in immune cells, immune function, the expression level of genes related to immune checkpoints, and TMB in high- and low-risk groups. Conclusion: This CRLs prognostic signature could predict clinical outcomes in patients with HCC as well as the efficacy of targeted and therapy immunotherapy.

KEYWORDS:

• Hepatocellular Carcinoma
• lncrnas
• cuproptosis
• prognostic signature
• immune microenvironment

Acknowledgements

We are very grateful to The Cancer Genome Atlas for providing data on patients with hepatocellular carcinoma.

Availability of data and materials

Data utilised in research were available in articles, supplementary files, and online database sites.

Author’s contribution

D.F. Guo and X.H. Wu conceived and designed this search. C.B. Huang gave administrative support. D.F. Guo and L.W. Fan acquired the needed data from the TCGA database. D.F. Guo, L.W. Fan, and H.H. Zeng analysed and interpreted the data. Finally, all authors composed and approved the manuscript.

Disclosure statement

No potential conflict of interest was reported by the authors.

Supplemental data

Supplemental data for this article can be accessed online at https://doi.org/10.1080/02648725.2023.2190640.

Additional information

Funding

This research has not received any funding support.

Notes on contributors

Ding-Fan Guo

Ding-Fan Guo is a resident physician in the Gastroenterology Department, First Affiliated Hospital of Gannan Medical University.

Lin-Wei Fan

Lin-Wei Fan is a PhD student in Key Laboratory of Jiangxi Province for Transfusion Medicine, First Affiliated Hospital of Nanchang University.

Hai-Hui Zeng

Hai-Hui Zeng is a resident physician in the Pneumology Department, First Affiliated Hospital of Gannan Medical University.

Cai-Bin Huang

Cai-Bin Huang is working as a professor in the Gastroenterology Department, First Affiliated Hospital of Gannan Medical University.

Xin-Huan Wu

Xin-Huan Wu is a doctor with rich clinical experience in the Gastroenterology Department, First Affiliated Hospital of Gannan Medical University.