Identification of Iron Metabolism-Related Gene Signatures for Predicting the Prognosis of Patients With Sarcomas

Abstract

Iron is one of the essential trace elements in the human body. An increasing amount of evidence indicates that the imbalance of iron metabolism is related to the occurrence and development of cancer. Here, we obtained the gene expression and clinical data of sarcoma patients from TCGA and the GEO database. The prognostic value of iron metabolism-related genes (IMRGs) in patients with sarcoma and the relationship between these genes and the immune microenvironment were studied by comprehensive bioinformatics analyses. Two signatures based on IMRGs were generated for the overall survival (OS) and disease-free survival (DFS) of sarcoma patients. At 3, 5, and 7 years, the areas under the curve (AUCs) of the OS signature were 0.708, 0.713, and 0.688, respectively. The AUCs of the DFS signature at 3, 5, and 7 years were 0.717, 0.689, and 0.702, respectively. Kaplan–Meier survival analysis indicated that the prognosis of high-risk patients was worse than that of low-risk patients. In addition, immunological analysis showed that there were different patterns of immune cell infiltration among patients in different clusters. Finally, we constructed two nomograms that can be used to predict the OS and DFS of sarcoma patients. The C-index was 0.766 (95% CI: 0.697–0.835) and 0.763 (95% CI: 0.706–0.820) for the OS and DFS nomograms, respectively. Both the ROC curves and the calibration plots showed that the two nomograms have good predictive performance. In summary, we constructed two IMRG-based prognostic models that can effectively predict the OS and DFS of sarcoma patients.

Divergent iron-regulatory states contribute to heterogeneity in breast cancer aggressiveness

“…Interestingly, ACO2 has been shown to promote colon cancer progression (69). Our results implicate ACO1 in breast cancer and add important nuance to the idea that cancer cells become "iron-addicted" (70)(71)(72)(73)(74). Therapies aiming at either removing or over-loading iron in the tumor microenvironment are both being explored (72,73).…”

A model based on eight iron metabolism-related genes accurately predicts acute myeloid leukemia prognosis

“…Growing evidence shows that aberrant iron metabolism participates in AML initiation, progression, and infiltration of immune cells to the microenvironment (Kennedy et al, 2014;Benadiba et al, 2017;Hagag et al, 2018). Numerous studies have implicated dysregulated expression of IMRGs in cancer progression (Li et al, 2020;Zhu et al, 2021;Song et al, 2022). Therefore, iron metabolism is a potential target for clinical diagnosis and treatment of AML.…”

Ferroptosis of CD163+ tissue-infiltrating macrophages and CD10+ PC+ epithelial cells in lupus nephritis

“…The iron metabolism gene list (70 genes) was extracted from the study by Li et al. ( 20 ). The oxidative phosphorylation gene list (83 genes) was extracted from the KEGG_OXIDATIVE_PHOSPHORYLATION gene set.…”

“…The fatty acid biosynthesis gene list (22 genes) and glutathione synthesis gene list (16 genes) were from the PathCards database (https://pathcards.genecards.org/). The iron metabolism gene list (70 genes) was extracted from the study by Li et al (20). The oxidative phosphorylation gene list (83 genes) was extracted from the KEGG_OXIDATIVE_PHOSPHORYLATION gene set.…”