Open AccessPrognostic and predictive role of a metabolic rate‐limiting enzyme signature in hepatocellular carcinoma
Author(s) -
Wang Zhangding,
Fu Yao,
Xia Anliang,
Chen Chen,
Qu Jiamu,
Xu Guifang,
Zou Xiaoping,
Wang Qiang,
Wang Shouyu
Publication year - 2021
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/cpr.13117
Subject(s) - nomogram , cohort , oncology , hepatocellular carcinoma , medicine , proportional hazards model , limiting , receiver operating characteristic , cohort study , mechanical engineering , engineering
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.