Abstract
Background: Long noncoding RNAs (lncRNAs) act as epigenetic regulators in the process of ferroptosis and iron metabolism. This study aimed to identify an iron metabolism-related lncRNA signature to predict osteosarcoma (OS) survival and the immune landscape. Methods: RNA-sequencing data and clinical information were obtained from the TARGET dataset. Univariate Cox regression and LASSO Cox analysis were used to develop an iron metabolism-related lncRNA signature. Consensus clustering analysis was applied to identify subtype-based prognosis-related lncRNAs. CIBERSORT was used to analyze the difference in immune infiltration and the immune microenvironment in the two clusters. Results: We identified 302 iron metabolism-related lncRNAs based on 515 iron metabolism-related genes. The results of consensus clustering showed the differences in immune infiltration and the immune microenvironment in the two clusters. Through univariate Cox regression and LASSO Cox regression analysis, we constructed an iron metabolism-related lncRNA signature that included seven iron metabolism-related lncRNAs. The signature was verified to have good performance in predicting the overall survival, immune-related functions, and immunotherapy response of OS patients between the high- and low-risk groups. Conclusion: We identified an iron metabolism-related lncRNA signature that had good performance in predicting survival outcomes and showing the immune landscape for OS patients. Furthermore, our study will provide valuable information to further develop immunotherapies of OS.
Highlights
Osteosarcoma (OS) is the most common primary solid malignancy of the bone in children and adolescents, and the overall incidence is ~4.8 per million worldwide (Lancia et al, 2019; Pingping et al, 2019)
Through univariate Cox regression analysis, we identified 30 iron metabolism-related Long noncoding RNAs (lncRNAs) whose expression levels were significantly associated (p < 0.05) with the overall survival of OS patients
According to the criteria |R| >0.5 and p-value
Summary
Osteosarcoma (OS) is the most common primary solid malignancy of the bone in children and adolescents, and the overall incidence is ~4.8 per million worldwide (Lancia et al, 2019; Pingping et al, 2019). Iron is an indispensable element involved in many cellular processes, such as DNA synthesis, ATP production, and oxygen transport (Brown et al, 2020; Forciniti et al, 2020). Iron metabolism is usually divided into distinct processes, including iron acquisition, efflux, storage, and regulation, which is regulated by a set of iron-dependent proteins (Torti & Torti, 2013). Ferroptosis is an iron-dependent form of regulated cell death caused by excess levels of reactive oxygen species (ROS) and lipid peroxidation products (Stockwell et al, 2017; Chen et al, 2021). Emerging evidence shows that triggering ferroptosis has anticancer potential for cancer therapy (Liang et al, 2019; Xu et al, 2019). Long noncoding RNAs (lncRNAs) act as epigenetic regulators in the process of ferroptosis and iron metabolism. This study aimed to identify an iron metabolism-related lncRNA signature to predict osteosarcoma (OS) survival and the immune landscape
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