A novel signature of combing cuproptosis- with ferroptosis-related genes for prediction of prognosis, immunologic therapy responses and drug sensitivity in hepatocellular carcinoma

Abstract

BackgroundOur study aimed to construct a novel signature (CRFs) of combing cuproptosis-related genes with ferroptosis-related genes for the prediction of the prognosis, responses of immunological therapy, and drug sensitivity of hepatocellular carcinoma (HCC) patients.MethodsThe RNA sequencing and corresponding clinical data of patients with HCC were downloaded from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), GSE76427, GSE144269, GSE140580, Cancer Cell Line Encyclopedia (CCLE), and IMvigor210 cohorts. CRFs was constructed using the least absolute shrinkage and selection operator (LASSO) algorithm. The analyses involved in the prognosis, response to immunologic therapy, efficacy of transcatheter arterial chemoembolization (TACE) therapy, and drug sensitivity were performed. Furthermore, the molecular function, somatic mutation, and stemness analyses were further performed between the low- and high-risk groups, respectively. In this study, the statistical analyses were performed by using the diverse packages of R 4.1.3 software and Cytoscape 3.8.0.ResultsCRFs included seven genes (G6PD, NRAS, RRM2, SQSTM1, SRXN1, TXNRD1, and ZFP69B). Multivariate Cox regression analyses demonstrated that CRFs were an independent risk factor for prognosis. In addition, these patients in the high-risk group presented with worse prognoses and a significant state of immunosuppression. Moreover, patients in the high-risk group might achieve greater outcomes after receiving immunologic therapy, while patients in the low-risk group are sensitive to TACE. Furthermore, we discovered that patients in the high-risk group may benefit from the administration of sunitinib. In addition, enhanced mRANsi and tumor mutation burden (TMB) yielded in the high-risk group. Additionally, the functions enriched in the low-risk group differed from those in the other group.ConclusionIn summary, CRFs may be regarded not only as a novel biomarker of worse prognosis, but also as an excellent predictor of immunotherapy response, efficacy of TACE and drug sensitivity in HCC, which is worthy of clinical promotion.

Metabolism-related signatures is correlated with poor prognosis and immune infiltration in hepatocellular carcinoma via multi-omics analysis and basic experiments

“…In addition, Wang and Zhao et al. found that G6PD could be used for building models of hepatocellular carcinoma ( 22 , 23 ). All of the above studies indicate that G6PD and the development of hepatocellular carcinoma are closely related.…”

Establishment and validation of a ferroptosis-related prognostic signature for hepatocellular carcinoma

“…TP53 has been shown to be a tumor suppressors in regulating metabolism of tumor cells ( 40 , 41 ). Nevertheless, HCC tissues with TP53 mutation could detect the vascular invasion and angiogenesis, and these tissues are characterized by hypodifferentiation ( 42 , 43 ). CTNNB1 gene encodes the protein β-catenin which has been found could promote immune escape and may affect the immunotherapy in HCC ( 44 ).…”

Copper metabolism and cuproptosis in human malignancies: Unraveling the complex interplay for therapeutic insights

“…Emerging evidence have provided a robust connection between iron- and copper-dependent cell death across many cancers. For instance, in hepatocellular carcinoma and lung adenocarcinoma, the reciprocity between regulators of ferroptosis and cuproptosis elucidates the tumor microenvironment, which ultimately governs prognosis and sensitivity for chemotherapeutics [ 132 , 133 ]. Apart from the association of cuproptosis and ferroptosis with cancer, further studies have significantly uncovered their interplay.…”