The ferroptosis and iron-metabolism signature robustly predicts clinical diagnosis, prognosis and immune microenvironment for hepatocellular carcinoma

Abstract

Background In this study, we comprehensively analyzed genes related to ferroptosis and iron metabolism to construct diagnostic and prognostic models and explore the relationship with the immune microenvironment in HCC. Methods Integrated analysis, cox regression and the least absolute shrinkage and selection operator (LASSO) method of 104 ferroptosis- and iron metabolism-related genes and HCC-related RNA sequencing were performed to identify HCC-related ferroptosis and iron metabolism genes. Results Four genes (ABCB6, FLVCR1, SLC48A1 and SLC7A11) were identified to construct prognostic and diagnostic models. Poorer overall survival (OS) was exhibited in the high-risk group than that in the low-risk group in both the training cohort (P < 0.001, HR = 0.27) and test cohort (P < 0.001, HR = 0.27). The diagnostic models successfully distinguished HCC from normal samples and proliferative nodule samples. Compared with low-risk groups, high-risk groups had higher TMB; higher fractions of macrophages, follicular helper T cells, memory B cells, and neutrophils; and exhibited higher expression of CD83, B7H3, OX40 and CD134L. As an inducer of ferroptosis, erastin inhibited HCC cell proliferation and progression, and it was showed to affect Th17 cell differentiation and IL-17 signaling pathway through bioinformatics analysis, indicating it a potential agent of cancer immunotherapy. Conclusions The prognostic and diagnostic models based on the four genes indicated superior diagnostic and predictive performance, indicating new possibilities for individualized treatment of HCC patients. Graphical abstract

Identification of Aging-Related Genes Associated With Clinical and Prognostic Features of Hepatocellular Carcinoma

“…Compared with low-risk patients, high-risk patients typically present with more aggressive characteristics, advanced stages, and higher mortality (all p < 0.05). Furthermore, the risk score exhibited better predictive capability than the conventional TNM stage and published risk scores (Fang and Chen, 2020;Liang et al, 2020;Tang et al, 2020;Yan et al, 2020).…”

A Prognostic Ferroptosis-Related lncRNAs Signature Associated With Immune Landscape and Radiotherapy Response in Glioma

“…Ferroptosis, a non-apoptotic form of PCD, has recently emerged as a topic of intensive research in the field of tumorigenesis and therapies. It has been reported that ferroptosis-related biomarkers are robust predictors of prognosis and antitumor efficacy for cancers ( Shi et al, 2019 ; Liang et al, 2020 ; Tang B. et al, 2020 ). Nevertheless, previous studies only focused on the ferroptosis-related genes encoding proteins involving in the regulation of ferroptosis.…”

Identification of Novel Prognostic Risk Signatures of Soft Tissue Sarcoma Based on Ferroptosis-Related Genes

“…In the enrichment analyses, we find that DEFRG were enriched in the immune-related pathways. A large number of studies have also shown that ferroptosis is closely related to tumor immunity (25)(26)(27). Therefore, we further studied the pattern of immune cell infiltration between different risk groups.…”