Prognostic Model and Nomogram Construction Based on a Novel Ferroptosis-Related Gene Signature in Lower-Grade Glioma

Background: Low-grade glioma (LGG) is considered a fatal disease for young adults, with overall survival widely ranging from 1 to 15 years depending on histopathologic and molecular subtypes. As a novel type of programmed cell death, ferroptosis was reported to be involved in tumorigenesis and devel...

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Autores principales: Junsheng Zhao, Zhengtao Liu, Xiaoping Zheng, Hainv Gao, Lanjuan Li
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Publicado: Frontiers Media S.A. 2021
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spelling oai:doaj.org-article:905917214b7d4faa9cb9a2ffa74ddcf72021-11-08T06:15:18ZPrognostic Model and Nomogram Construction Based on a Novel Ferroptosis-Related Gene Signature in Lower-Grade Glioma1664-802110.3389/fgene.2021.753680https://doaj.org/article/905917214b7d4faa9cb9a2ffa74ddcf72021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fgene.2021.753680/fullhttps://doaj.org/toc/1664-8021Background: Low-grade glioma (LGG) is considered a fatal disease for young adults, with overall survival widely ranging from 1 to 15 years depending on histopathologic and molecular subtypes. As a novel type of programmed cell death, ferroptosis was reported to be involved in tumorigenesis and development, which has been intensively studied in recent years.Methods: For the discovery cohort, data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) were used to identify the differentially expressed and prognostic ferroptosis-related genes (FRGs). The least absolute shrinkage and selection operator (LASSO) and multivariate Cox were used to establish a prognostic signature with the above-selected FRGs. Then, the signature was developed and validated in TCGA and Chinese Glioma Genome Atlas (CGGA) databases. By combining clinicopathological features and the FRG signature, a nomogram was established to predict individuals’ one-, three-, and five-year survival probability, and its predictive performance was evaluated by Harrell’s concordance index (C-index) and calibration curves. Enrichment analysis was performed to explore the signaling pathways regulated by the signature.Results: A novel risk signature contains seven FRGs that were constructed and were used to divide patients into two groups. Kaplan–Meier (K−M) survival curve and receiver-operating characteristic (ROC) curve analyses confirmed the prognostic performance of the risk model, followed by external validation based on data from the CGGA. The nomogram based on the risk signature and clinical traits was validated to perform well for predicting the survival rate of LGG. Finally, functional analysis revealed that the immune statuses were different between the two risk groups, which might help explain the underlying mechanisms of ferroptosis in LGG.Conclusion: In conclusion, this study constructed a novel and robust seven-FRG signature and established a prognostic nomogram for LGG survival prediction.Junsheng ZhaoZhengtao LiuXiaoping ZhengHainv GaoLanjuan LiFrontiers Media S.A.articleferroptosislower-grade gliomaprognostic signatureTCGACGGAimmune statusesGeneticsQH426-470ENFrontiers in Genetics, Vol 12 (2021)
institution DOAJ
collection DOAJ
language EN
topic ferroptosis
lower-grade glioma
prognostic signature
TCGA
CGGA
immune statuses
Genetics
QH426-470
spellingShingle ferroptosis
lower-grade glioma
prognostic signature
TCGA
CGGA
immune statuses
Genetics
QH426-470
Junsheng Zhao
Zhengtao Liu
Xiaoping Zheng
Hainv Gao
Lanjuan Li
Prognostic Model and Nomogram Construction Based on a Novel Ferroptosis-Related Gene Signature in Lower-Grade Glioma
description Background: Low-grade glioma (LGG) is considered a fatal disease for young adults, with overall survival widely ranging from 1 to 15 years depending on histopathologic and molecular subtypes. As a novel type of programmed cell death, ferroptosis was reported to be involved in tumorigenesis and development, which has been intensively studied in recent years.Methods: For the discovery cohort, data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) were used to identify the differentially expressed and prognostic ferroptosis-related genes (FRGs). The least absolute shrinkage and selection operator (LASSO) and multivariate Cox were used to establish a prognostic signature with the above-selected FRGs. Then, the signature was developed and validated in TCGA and Chinese Glioma Genome Atlas (CGGA) databases. By combining clinicopathological features and the FRG signature, a nomogram was established to predict individuals’ one-, three-, and five-year survival probability, and its predictive performance was evaluated by Harrell’s concordance index (C-index) and calibration curves. Enrichment analysis was performed to explore the signaling pathways regulated by the signature.Results: A novel risk signature contains seven FRGs that were constructed and were used to divide patients into two groups. Kaplan–Meier (K−M) survival curve and receiver-operating characteristic (ROC) curve analyses confirmed the prognostic performance of the risk model, followed by external validation based on data from the CGGA. The nomogram based on the risk signature and clinical traits was validated to perform well for predicting the survival rate of LGG. Finally, functional analysis revealed that the immune statuses were different between the two risk groups, which might help explain the underlying mechanisms of ferroptosis in LGG.Conclusion: In conclusion, this study constructed a novel and robust seven-FRG signature and established a prognostic nomogram for LGG survival prediction.
format article
author Junsheng Zhao
Zhengtao Liu
Xiaoping Zheng
Hainv Gao
Lanjuan Li
author_facet Junsheng Zhao
Zhengtao Liu
Xiaoping Zheng
Hainv Gao
Lanjuan Li
author_sort Junsheng Zhao
title Prognostic Model and Nomogram Construction Based on a Novel Ferroptosis-Related Gene Signature in Lower-Grade Glioma
title_short Prognostic Model and Nomogram Construction Based on a Novel Ferroptosis-Related Gene Signature in Lower-Grade Glioma
title_full Prognostic Model and Nomogram Construction Based on a Novel Ferroptosis-Related Gene Signature in Lower-Grade Glioma
title_fullStr Prognostic Model and Nomogram Construction Based on a Novel Ferroptosis-Related Gene Signature in Lower-Grade Glioma
title_full_unstemmed Prognostic Model and Nomogram Construction Based on a Novel Ferroptosis-Related Gene Signature in Lower-Grade Glioma
title_sort prognostic model and nomogram construction based on a novel ferroptosis-related gene signature in lower-grade glioma
publisher Frontiers Media S.A.
publishDate 2021
url https://doaj.org/article/905917214b7d4faa9cb9a2ffa74ddcf7
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AT xiaopingzheng prognosticmodelandnomogramconstructionbasedonanovelferroptosisrelatedgenesignatureinlowergradeglioma
AT hainvgao prognosticmodelandnomogramconstructionbasedonanovelferroptosisrelatedgenesignatureinlowergradeglioma
AT lanjuanli prognosticmodelandnomogramconstructionbasedonanovelferroptosisrelatedgenesignatureinlowergradeglioma
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