Journal
CELL PROLIFERATION
Volume 54, Issue 10, Pages -Publisher
WILEY
DOI: 10.1111/cpr.13117
Keywords
hepatocellular carcinoma; metabolism; prognosis; rate-limiting enzymes; signature
Categories
Funding
- Fundamental Research Funds for the Central Universities [021414380439]
- natural science foundation of Jiangsu Province [BK20200132]
- National Natural Science Foundation of China [81773383, 81903085, 82073114]
- Science Foundation for Distinguished Young Scholars of Jiangsu Province [BK20170047]
- China Postdoctoral Science Foundation [2019M651808, 2020M681562, 2020T130291]
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This study aimed to elucidate the comprehensive model of metabolic rate-limiting enzymes associated with the prognosis of hepatocellular carcinoma. A classifier based on three rate-limiting enzymes (RRM1, UCK2 and G6PD) was found to serve as an independent prognostic factor. Combining clinical risk score with signature risk score significantly improved the prediction accuracy of individual outcomes, highlighting the prognostic value of rate-limiting enzymes in guiding clinical management and treatment decisions for HCC.
Objectives Abnormal expression of metabolic rate-limiting enzymes drives the occurrence and progression of hepatocellular carcinoma (HCC). This study aimed to elucidate the comprehensive model of metabolic rate-limiting enzymes associated with the prognosis of HCC. Materials and Methods HCC animal model and TCGA project were used to screen out differentially expressed metabolic rate-limiting enzyme. Cox regression, least absolute shrinkage and selection operation (LASSO) and experimentally verification were performed to identify metabolic rate-limiting enzyme signature. The area under the receiver operating characteristic curve (AUC) and prognostic nomogram were used to assess the efficacy of the signature in the three HCC cohorts (TCGA training cohort, internal cohort and an independent validation cohort). Results A classifier based on three rate-limiting enzymes (RRM1, UCK2 and G6PD) was conducted and serves as independent prognostic factor. This effect was further confirmed in an independent cohort, which indicated that the AUC at year 5 was 0.715 (95% CI: 0.653-0.777) for clinical risk score, whereas it was significantly increased to 0.852 (95% CI: 0.798-0.906) when combination of the clinical with signature risk score. Moreover, a comprehensive nomogram including the signature and clinicopathological aspects resulted in significantly predict the individual outcomes. Conclusions Our results highlighted the prognostic value of rate-limiting enzymes in HCC, which may be useful for accurate risk assessment in guiding clinical management and treatment decisions.
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