Prognostic model development using novel genetic signature associated with adenosine metabolism and immune status for patients with hepatocellular carcinoma

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Abstract
The high mortality rate of hepatocellular carcinoma (HCC) is partly due to advanced diagnosis, emphasizing the need for effective predictive tools in HCC treatment. The aim of this study is to propose a novel prognostic model for HCC based on adenosine metabolizing genes and explore the potential relationship between them. Regression analysis was performed to identify differentially expressed genes associated with adenosine metabolism in HCC patients using RNA sequencing data obtained from a public database. Adenosine metabolism-related risk score (AMrisk) was derived using the least absolute shrinkage and selection operator (LASSO) Cox regression and verified using another database. Changes in adenosine metabolism in HCC were analyzed using functional enrichment analysis and multiple immune scores. The gene expression levels in patient samples were validated using quantitative reverse transcription polymerase chain reaction. Thirty adenosine metabolism-related differentially expressed genes were identified in HCC, and six genes (ADA, P2RY4, P2RY6, RPIA, SLC6A3, and VEGFA) were used to calculate the AMrisk score; the higher the risk scores, the lower the overall survival. Moreover, immune infiltration activation and immune checkpoints were considerably higher in the high-risk group. Additional in vitro experiments validated the enhanced expression of these six genes in HCC. The established predictive model demonstrated that adenosine metabolism-related genes was significantly associated with prognosis in HCC patients.
Funding Information
  • National Natural Science Foundation of China (82200577 and 82173241, 82200577 and 82173241)
  • Key Research and Development Projects of Shaanxi Province (2023-ZDLSF-33)
  • Science and Technology Innovation Team of Shaanxi Province (2024RS-CXTD-79)

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