Identification of a ferroptosis-related lncRNA signature with prognosis for Wilms tumor

• Published in: Translational pediatrics Vol. 10; no. 10; pp. 2418 - 2431
• Main Authors: Liu, Hengchen, Zhang, Mingzhao, Zhang, Tingting, Shi, Manyu, Lu, Wenjun, Yang, Shulong, Cui, Qingbo, Li, Zhaozhu
• Format: Journal Article
• Language: English
• Published: China AME Publishing Company 01.10.2021
• Subjects: Original; TARGET; lncRNAs; ferroptosis; Wilms tumor (WT); prognosis
• ISSN: 2224-4344; 2224-4336; 2224-4344
• DOI: 10.21037/tp-21-211

Wilms tumor (WT) is a widespread urologic tumor in children. Ferroptosis, on the other hand, is a novel form of cell death associated with tumor development. In this study, we aim to explore the predictability of ferroptosis-related biomarkers in estimating prognosis in WT patients. To determine a link between ferroptosis-related gene expression and WT prognosis, we first collected RNA sequencing data and clinical information, involving 124 WT and 6 healthy tissue samples, from the TARGET database. Next, we screened the collected information for ferroptosis-related long non-coding RNA using Cox regression analysis, and constructed a signature model, as well as a nomogram, related to prognosis. Finally, we explored a potential link between ferroptosis-related lncRNA and tumor immunity and screened for possible immune checkpoints. We constructed a WT prognosis prediction signature containing 12 ferroptosis-related lncRNAs. The area under the curves values, from the ROC curves, predicting overall survival rates at the 1, 3-, and 5-year timepoints were 0.775, 0.867, and 0.891 respectively. Moreover, we generated a nomogram, using clinical features and risk scores, carrying a C-index value of 0.836, which suggested a high predictive value. We also demonstrated significant differences in tumor immunity between low- and high-risk WT patients, particularly in the presence of B cells, NK cells, Th1 cells, Treg cells, inflammation promoting, and type I and II IFN responses. In addition, we showed that immune checkpoints like , , , , , and can serve as potential therapeutic targets for WT. Based on our analyses, we generated a ferroptosis-related lncRNA signature that can both estimate prognosis of WT patients and may provide basis for future WT therapy.