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Original Research

Identification of a Prognostic Index Based on a Metabolic-Genomic Landscape Analysis of Hepatocellular Carcinoma (HCC)

, , , &
Pages 5683-5698 | Published online: 15 Jul 2021
 

Abstract

Background

Metabolic disorders have attracted increasing attention from scientists who conduct research on various tumours, especially hepatocellular carcinoma (HCC). The purpose of this study was to assess the prognostic significance of metabolism in HCC.

Methods

The expression profiles of metabolism-related genes (MRGs) of 349 surviving HCC patients were extracted from The Cancer Genome Atlas (TCGA) database. Subsequently, a series of biomedical computational algorithms were used to identify a seven-MRG signature as a prognostic model. GSEA indicated the function and pathway enrichment of these MRGs. Then, drug sensitivity analysis was used to identify the hub gene, which was tested using IHC staining.

Results

A total of 420 differential MRGs and 116 differentially expressed transcription factors (TFs) were identified in HCC patients based on data from the TCGA database. The GO and KEGG enrichment analyses indicated that metabolic disturbance might be involved in the development of HCC. LASSO regression analysis was used to construct a seven-MRG signature (DHDH, ENO1, G6PD, LPCAT1, PDE6D, PIGU and PPAT) that could predict the prognosis of HCC patients. GSEA revealed the functional and pathway enrichment of these seven MRGs. Then, drug sensitivity analysis indicated that G6PD might play a key role in the prognosis of HCC by promoting chemoresistance. Finally, we used IHC staining to demonstrate the relationship between G6PD expression levels and clinical parameters in HCC patients.

Conclusion

The results of this study provide a potential method for predicting the prognosis of HCC patients and avenues for further studies of HCC metabolism. Moreover, the function of G6PD may play a key role in the development and progression of HCC.

Acknowledgments

The authors would like to thank the DAVID, GTEX and TCGA databases for the availability of the data.

Data Sharing Statement

The data used to support the findings of this study are available from the corresponding author upon request.

Ethics Approval and Consent to Participate

The collection and use of tissues followed the procedures according to the ethical standards as formulated in the Helsinki Declaration. Written informed consent was obtained from each patient, which was approved by the research ethics committee of the University of South China.

Consent for Publication

Written informed consent for publication was obtained from all participants.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.