摘要
Background:As the most common iron metabolism and storage organ,the specific regulatory mechanism and prognostic relevance of hepatocellular carcinoma(HCc)need further study.Objective:We aimed to perform a multi-omics integration and a ferroptosis-associated signature of HCC.Methods:Gene Expression Omnibus was searched for available data with ferroptosis inducers,and three independent datasets(GSE104462,GSE112384,and GSE142591)were collected.Multi-omic data with available clinical information of TCGA-LIHC and CHCC were retrieved from the Cancer Genome Atlas(TCGA,http://cancergenome.nih.gov/)and iProX database(www.iprox.org,IPx0000937000).Integrated multi-omics analyses revealed the difference among biological functions,the activation status of key signaling pathways,tumor microenvironment,and sorafenib resistance in HCC.Single-sample gene set enrichment analysis(ssGSEA)identified a novel panel associated with clinical and molecular attributes,including survival,immune microenvironment,sorafenib resistance,genetic profile,liver-specific proteome,and phosphoproteome.Results:We performed a multi-omics integrationfor ferroptosis-associated characterization of HCC using paired tumor and adjacent liver tissues from 370 samples of TCGA.We proposed a novel panel including twelve genes that could reflect the prognosis and capacity of ferroptosis(ATAD2,DTL,DUT,E2F2,GINS2,FOXK1,MCM4,MCM5,MTHFD1,PHF19,POLA1,THOC6).Samples with high ferroptosis prognostic scores suggested significantly inferior survival(P=0.0028),a lower degree of ferroptosis(P<0.001),and greater ferroptosis induction capacity(P<0.001).Conclusion:The score in our study revealed the inherent state and further potential of ferroptosis in tumor cells,which also distinct features in tumor metabolism,microenvironment,clinical phenotype,and potential therapeutics.
基金
supported by the Xingtai Key Research and Development(R&D)program(2020zC232).