Prognostic significance of pyrimidine metabolism-related genes as risk biomarkers in hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC), as a malignancy derived from liver tissue, is typically associated with poor prognosis. Increasing evidence suggests a connection between pyrimidine metabolism and HCC progression. The purpose of this study was to establish a model applied to the prediction of HCC patients’ overall survival. Transcriptomic data of HCC patients were downloaded from The Cancer Genome Atlas (TCGA) website. Pyrimidine metabolism-related genes (PMRGs) were collected from the Gene Set Enrichment Analysis (GSEA) website. Differential gene expression analysis was carried out on the HCC data, followed by an intersection of the differentially expressed genes (DEGs) and PMRGs. Subsequently, a prognostic model incorporating nine genes was established using univariate/multivariate Cox regression and Least absolute shrinkage and selection operator (LASSO) regression. Survival analysis demonstrated that the high-risk group defined by this model had considerably shorter overall survival than the low-risk group in both TCGA and Gene Expression Omnibus (GEO) datasets. Receiver operating characteristic (ROC) analysis indicated the good predictive capability of the model. CIBERSORT and single sample gene set enrichment analysis (ssGSEA) algorithms revealed significantly higher levels of Macrophages M0 and lower levels of natural killer (NK)_cells in the high-risk group compared to the low-risk group. The immunophenoscore (IPS) and the tumor immune dysfunction and exclusion (TIDE) score demonstrated that the model could significantly differentiate patients who would be more suitable for immunotherapy. Moreover, the CellMiner database was utilized to predict anti-tumor drugs significantly associated with the model genes. Collectively, the potential prognostic significance of pyrimidine metabolism in HCC was revealed in this study. The prognostic model aids in evaluating the survival time and immune status of HCC patients.

Keywords:

• Hepatocellular carcinoma
• pyrimidine metabolism
• prognosis
• immune
• The Cancer Genome Atlas

Consent for publication

All authors consent to submit the manuscript for publication.

Authors contributions

Conceptualization: Lili Shi and Jie Lu

Data curation: Caiming Zhang and Fabiao Zhang

Formal Analysis: Caiming Zhang and Jie Lu

Funding acquisition: Miaoguo Cai

Writing: Lili Shi and Jie Lu

Supervision: Jie Lu and Fabiao Zhang

Data availability statement

The data and materials in the current study are available from the corresponding author on reasonable request.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This study was sponsored by Health Science and Technology Program of Zhejiang Provincial (2022KY1377).