A novel ferroptosis phenotype-related clinical-molecular prognostic signature for hepatocellular carcinoma

Tuo Deng, Bingren Hu, Chen Jin, Yifan Tong, Jungang Zhao, Zhehao Shi, Tan Zhang, Liming Deng, Zhifu Sun, Gang Chen, Yi Wang

Research output: Contribution to journalArticlepeer-review


Ferroptosis is a newly identified cell death mechanism and potential biomarker for hepatocellular carcinoma (HCC) therapy; however, its clinical relevance and underlying mechanism remain unclear. In this study, transcriptome and methylome data from 374 HCC cases were investigated for 41 ferroptosis-related genes to identify ferroptosis activity-associated subtypes. These subtypes were further investigated for associations with clinical and pathological variables, gene mutation landscapes, deregulated pathways and tumour microenvironmental immunity. A gene expression signature and predictive model were developed and validated using an additional 232 HCC cases from another independent cohort. Two distinct ferroptosis phenotypes (Ferroptosis-H and Ferroptosis-L) were identified according to ferroptosis gene expression and methylation in the patients with HCC. Patients with the Ferroptosis-H had worse overall and disease-specific survival, and the molecular subtypes were significantly associated with different clinical characteristics, mRNA expression patterns, tumour mutation profiles and microenvironmental immune status. Furthermore, a 15-gene ferroptosis-related prognostic model (FPM) for HCC was developed and validated which demonstrated accurate risk stratification ability. A nomogram included the FPM risk score, ECOG PS and hepatitis B status was developed for eventual clinical translation. Our results suggest that HCC subtypes defined by ferroptosis gene expression and methylation may be used to stratify patients for clinical decision-making.

Original languageEnglish (US)
Pages (from-to)6618-6633
Number of pages16
JournalJournal of Cellular and Molecular Medicine
Issue number14
StatePublished - Jul 2021


  • co-expression network
  • ferroptosis
  • hepatocellular carcinoma
  • prognostic signature
  • risk-stratification

ASJC Scopus subject areas

  • Molecular Medicine
  • Cell Biology


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